Skip to main content
SpringerLink
Log in

Altered Major Histocompatibility Complex Proteins and Peptides for the Induction of Tolerance After Organ Transplantation

  • Review Article
  • Immunology-Based Agents
  • Published:
BioDrugs Aims and scope Submit manuscript

Summary

Transplantation tolerance is defined as permanent acceptance of an allograft without the need for nonspecific immunosuppressants, which predispose patients to infectious and neoplastic complications. Our approach uses chemically modified antigenic proteins to modify the first signal that triggers allorecognition. The first signal, which is generated by the trimolecular interaction between the T cell receptor, the antigen-presenting major histocompatibility complex (MHC) protein and the antigenic peptide, is distinguished from a second signal that results from the co-stimulatory interactions between T lymphocytes and antigen-presenting cells and the third signal that results from the stimulatory effects of cytokines.

Previous studies in animal models have utilised pretransplant inoculation of the recipient with various types of donor-type cells, such as erythrocyte, bone marrow, transfectant or transgenic cells, or extracted transplantation antigens, which have been prepared by sonication, autolysis/proteolysis, detergent treatment or salt (3 mol/L KCl) extraction, which appears to be the most efficient method. Antigens extracted from natural cells induce tolerance in animal models when administered in pretreatment regimens via the intrathymic route (in conjunction with T cell depletion) or via the intravenous route (after preconditioning by total lymphoid irradiation).

Exposure to synthetic allopeptides representing sequences from the hypervariable or the constant regions of either class I or class II MHC molecules produces variable effects on in vivo and in vitro alloimmune reactions. In addition to the interactions between peptides and MHC proteins and/or T cell receptor sites, at least some peptides act by binding to receptors of the heat shock protein family, thereby increasing intracellular calcium concentrations without inducing costimulatory signals, and/or by interacting directly with unique surface receptors on natural killer cells. However, several factors intrinsic to peptides may limit their use for tolerance induction in vivo. First, peptides are rapidly cleared by non-immunological mechanisms from the circulation, requiring the use of large quantities. Second, peptides are unable to contact the host system in a fashion that reflects the immunogenicity/tolerogenicity of the epitope on the native molecules. Third, peptides are unable to be processed by antigen-presenting cells.

Our approach to tolerance induction uses allochimaeric MHC proteins, which are constructed by engrafting selected donor-type tolerogenic epitopes onto host-type MHC molecular backbones. When delivered in rat models via the intrathymic, intraportal or oral gavage route, allochimaeric class I MHC molecules induce immunodominant responses, namely they overwhelm all other responses toward foreign epitopes. Although most peritransplant antigen treatment regimens require concomitant administration of subtherapeutic doses of nonspecific immunosuppressants, some constructs induce tolerance without adjunctive immunosuppressive therapy. One critical requirement for tolerance induction by allochimaeric MHC antigens is the presence of host rather than third-party flanking amino acid sequences. The allochimaeric sequences seem to steer the host response toward tolerance by directly binding to immune cell receptors that deliver a ‘self’ signal (T cell receptor hypothesis), by directing endosomal catheptic activity to yield tolerogenic rather than immunogenic peptides (peptide hypothesis), or by altering the interactions in the tri-molecular complex, thereby interfering with the usual participation of the MHC molecule on the antigen-presenting cell (supertolerogen hypothesis).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature 1953; 172: 603–6

    Article  PubMed  CAS  Google Scholar 

  2. Krensky AM, Weiss A, Crabtree G, et al. Mechanism of disease: T lymphocyte-antigen interactions in transplant rejection. N Engl J Med 1990; 322: 510–7

    Article  PubMed  CAS  Google Scholar 

  3. Bjorkman PJ, Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem 1990; 59: 253–88

    Article  PubMed  CAS  Google Scholar 

  4. Bjorkman PJ, Saper MA, Samraoui B, et al. Structure of the human class I histocompatibility antigen HLA-A2. Nature 1987; 329: 506–12

    Article  PubMed  CAS  Google Scholar 

  5. Madden DR, Gorga HC, Strominger JL, et al. The three-dimensional structure of HLA-B27 at 2.1 Å resolution suggests a general mechanism for tight peptide binding to MHC. Cell 1992; 70: 1035–44

    Article  PubMed  CAS  Google Scholar 

  6. Falk K, Rotzschke O, Rammensee HG. Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature 1990; 348: 248–51

    Article  PubMed  CAS  Google Scholar 

  7. Urban RG, Chicz RM, Lane WS, et al. A subset of HLA-B27 molecules contains peptides much longer than nonamers. Proc Natl Acad sci USA 1994; 91: 1534–8

    Article  PubMed  CAS  Google Scholar 

  8. Brown JH, Jardetzky TS, Gorge JC, et al. The three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993; 364: 33–9

    Article  PubMed  CAS  Google Scholar 

  9. Garboczi DN, Ghosh P, Utz U, et al. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 1996; 384: 134–41

    Article  PubMed  CAS  Google Scholar 

  10. Adorini L. Selective suppression of T-cell activation by administration of MHC class-II binding peptides. Transplant Proc 1992; 24: 14

    PubMed  CAS  Google Scholar 

  11. Wingren AG, Parra E, Varga M, et al. T cell activation pathways: B7, LFA-3, and ICAM-1 shape unique T cell profiles. Crit Rev Immunol 1995; 15: 235–53

    Article  PubMed  CAS  Google Scholar 

  12. Cosimi AB, Delmonico FL, Wright KJ, et al. Prolonged survival of nonhuman primate renal allograft recipients treated only with anti-CD4 monoclonal antibody. Surgery 1990; 108: 406–10

    PubMed  CAS  Google Scholar 

  13. Isobe M, Yagita H, Okumura K, et al. Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science 1992; 255: 1125–7

    Article  PubMed  CAS  Google Scholar 

  14. Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996; 14: 233–58

    Article  PubMed  CAS  Google Scholar 

  15. Larsen CP, Ritchie SC, Pearson TC. Functional expression of the costimulatory molecule, B7/BB1, on murine dendritic cell populations. J Exp Med 1992; 176: 1215–20

    Article  PubMed  CAS  Google Scholar 

  16. Judge TA, Tang A, Spain LM, et al. The in. vivo mechanism of action of CTLA4 Ig. J Immunol 1996; 156: 2294–9

    PubMed  CAS  Google Scholar 

  17. Sayegh MH, Akalin E, Hancock WW, et al. CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J Exp Med 1995; 181: 1869–74

    Article  PubMed  CAS  Google Scholar 

  18. Fukaura H, Kent SC, Pietrusewicz MJ, et al. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-betal-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. J Clin Invest 1996; 98: 70–7

    Article  PubMed  CAS  Google Scholar 

  19. Davies JD, Martin G, Philips J, et al. T cell regulation in adult transplantation tolerance. J Immunol 1996; 157: 529–33

    PubMed  CAS  Google Scholar 

  20. Dallman MJ, Shiho D, Page TM, et al. Peripheral tolerance to alloantigen results from altered regulation of the interleukin 2 pathway. J Exp Med 1991; 173: 79–87

    Article  PubMed  CAS  Google Scholar 

  21. Shirwan H, Learner M, Wang HK, et al. Peptides derived from α-helices of allogeneic class I major histocompatibility complex antigens are potent inducers of CD4+ and CD8+ T cell and B cell responses after cardiac allograft rejection. Transplantation 1995; 59: 401–10

    PubMed  CAS  Google Scholar 

  22. Hunt DF, Michel H, Dickinson TA, et al. Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad. Science 1992; 256: 1817–20

    Article  PubMed  CAS  Google Scholar 

  23. Sayegh MH, Watschinger B, Carpenter CB. Mechanism of T cell recognition of alloantigen: the role of peptide. Transplantation 1994; 57: 1295–302

    Article  PubMed  CAS  Google Scholar 

  24. Gallon L, Watschinger B, Murphy B, et al. The indirect pathway of allorecognition: the occurrence of self-restricted T cell recognition of allo-MHC peptides early in acute renal allograft rejection and its inhibition by conventional immunosuppression. Transplantation 1995; 59: 612–6

    PubMed  CAS  Google Scholar 

  25. Lee RS, Grusby MJ, Glimcher LH, et al. Indirect recognition by helper cells can induce donor-specific cytotoxic T lymphocyte in. vivo. J Exp Med 1994; 179: 865–72

    Article  PubMed  CAS  Google Scholar 

  26. Benham AM, Sawyer GJ, Fabre JW. Indirect T cell allorecognition of donor antigens contributes to the rejection of vascularized kidney allografts. Transplantation 1995; 59: 1028–32

    Article  PubMed  CAS  Google Scholar 

  27. Mueller DL, Jenkins MK, Schartz RH. Clonal expansion versus functional clonal inactivation: a co-stimulatory signaling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol 1989; 7: 445–80

    Article  PubMed  CAS  Google Scholar 

  28. Sundstrom JB, Ansari AA. Comparative study of the role of professional versus semiprofessional or nonprofessional antigen presenting cells in the rejection of vascularized organ allografts. Transplant Immunol 1995; 3: 273–89

    Article  CAS  Google Scholar 

  29. Weiss A, Littman DR. Signal transduction by lymphocyte antigen receptors. Cell 1994; 76: 263–74

    Article  PubMed  CAS  Google Scholar 

  30. Chan AC, Iwashima M, Turck CW, et al. ZAP-70: a 70kd protein-tyrosine kinase that associates with TCR δ chain. Cell 1992; 71: 649–62

    Article  PubMed  CAS  Google Scholar 

  31. Liu J, Farmer JD, Lane WS. Calcineurin is a common target of cyclophilin-cyclosporine A and FKBP-FK506 complex. Cell 1991; 66: 807–15

    Article  PubMed  CAS  Google Scholar 

  32. Flanagan WM, Corthesy B, Bram RJ. Nuclear association of a T cell transcription factor blocked by FK506 and cyclosporin A. Nature 1991; 352: 803–7

    Article  PubMed  CAS  Google Scholar 

  33. Morris PJ, Ting A, Stocker JW. Leukocyte antigens in renal transplantation: the paradox of blood transfusion in renal transplantation. Med J Aust 1968; 2: 1088–90

    PubMed  CAS  Google Scholar 

  34. Dossetor JB, MacKinnon KJ, Gault MH, et al. Cadaveric kidney transplants. Transplantation 1967; 5: 844–53

    Article  PubMed  Google Scholar 

  35. Opelz G, Senger DPS, Mickey MR, et al. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc 1973; 5: 253–9

    PubMed  CAS  Google Scholar 

  36. Halasz NA, Orloff MJ. Antigen pretreatment and mechanisms of the resulting temporary tolerance. Proc Soc Exp Biol Med 1964; 116: 987–90

    PubMed  CAS  Google Scholar 

  37. Fabre JW, Morris PJ. The effect of donor strain blood pretreatment on renal allograft rejection in rats. Transplantation 1972; 14: 608–17

    Article  PubMed  CAS  Google Scholar 

  38. Wood KJ, Evins J, Morris PJ. Suppression of renal allograft rejection in the rat by class I antigen on purified erythrocytes. Transplantation 1985; 39: 56–62

    Article  PubMed  CAS  Google Scholar 

  39. Monaco AP, Wood ML, Maki T, et al. Future strategies in immunosuppression: induction of unresponsiveness to organ allografts in clinical transplantation. Transplant Proc 1989; 21: 3939–42

    PubMed  CAS  Google Scholar 

  40. Wood ML, Orosz CG, Gottschalk R, et al. The effect of injection of donor bone marrow on the frequency of donor-reactive CTL in antilymphocyte serum-treated, grafted mice. Transplantation 1992; 54: 665–71

    Article  PubMed  CAS  Google Scholar 

  41. Rigney ME, Gignac MR, Gritsch HA, et al. Graft hyporeactivity induced by donor-specific bone marrow. Transplantation 1996; 62: 1601–5

    Article  PubMed  CAS  Google Scholar 

  42. Thomas JM, Carver M, Cunningham P. Promotion of incompatible allograft acceptance in rhesus monkeys given post-transplant antithymocyte globulin and donor bone marrow. Transplantation 1987; 43: 332–8

    Article  PubMed  CAS  Google Scholar 

  43. McDaniel DO, Naftilan J, Hulvey K, et al. Peripheral blood chimerism in renal allograft recipients transfused with donor bone marrow. Transplantation 1994; 57: 852–6

    Article  PubMed  CAS  Google Scholar 

  44. Zeevi A, Pavlick M, Bannas R, et al. Three years of follow-up of bone marrow augmented organ transplant recipients: the impact on donor-specific immune modulation [abstract 319]. Am Soc Transpl Phys 1996: 164

  45. Ricordi C, Karatzas T, Nery J, et al. High-dose donor bone marrow infusions to enhance allograft survival. Transplantation 1997; 63: 7–11

    Article  PubMed  CAS  Google Scholar 

  46. Madsen JC, Superina RA, Wood KJ, et al. Immunological unresponsiveness induced by recipient cells transfected with donor MHC genes. Nature 1988; 332: 161–4

    Article  PubMed  CAS  Google Scholar 

  47. Fraser CC, Sykes M, Lee RS, et al. Specific unresponsiveness to a retrovirally-transferred class I antigen is controlled through the helper pathway. J Immunol 1995; 154: 1587–95

    PubMed  CAS  Google Scholar 

  48. Saitovitch D, Morris PJ, Wood KJ. Recipient cells expressing single donor MHC locus products can substitute for donor-specific transfusion in the induction of transplantation tolerance when pretreatment is combined with anti-CD4 monoclonal antibody. Transplantation 1996; 61: 1532–8

    Article  PubMed  CAS  Google Scholar 

  49. Wong W, Morris PJ, Wood KJ. Syngeneic bone marrow expressing a single donor class I MHC molecule permits acceptance of a fully allogeneic cardiac allograft. Transplantation 1996; 62: 1462–8

    Article  PubMed  CAS  Google Scholar 

  50. Arnold B, Martin M, Jatsch L, et al. Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane-bound alloantigen. Proc Natl Acad sci USA 1990; 87: 1762–6

    Article  PubMed  CAS  Google Scholar 

  51. Medawar PB. The use of antigenic tissue to weaken the immunological reaction against skin homografts in mice. Transplantation 1963; 1: 21–38

    Article  PubMed  CAS  Google Scholar 

  52. Kahan BD. Isolation of a soluble transplantation antigen. Proc Natl Acad sci USA 1965; 53: 153–61

    Article  PubMed  CAS  Google Scholar 

  53. Kahan BD, Reisfeld RA, Pellegrino MA, et al. Water-soluble human transplantation antigen. Proc Natl Acad sci USA 1968; 61: 897–904

    Article  PubMed  CAS  Google Scholar 

  54. Nathenson SG, Davies DAL. Solubilization and partial purification of mouse histocompatibility antigens from a membranous lipoprotein fraction. Proc Natl Acad sci USA 1966; 56: 476–83

    Article  PubMed  CAS  Google Scholar 

  55. Nathenson SG, Shimada A. Papain solubilization of mouse H-2 isoantigen: an improved method of wide applicability. Transplantation 1968; 6: 662–5

    Article  Google Scholar 

  56. Kandutsch AA, Stimpfling JH. Partial purification of tissue isoantigens from a mouse sarcoma. Transplantation 1963; 1: 201–16

    Article  Google Scholar 

  57. Reisfeld RA, Kahan BD. Biological and chemical characterization of human histocompatibility antigens. Fed Proc 1970; 29: 2034–40

    PubMed  CAS  Google Scholar 

  58. LeGrue SJ, Macek CM, Kahan BD. Noncytolytic extraction of murine tumor-specific transplantation antigens with the nonionic detergent octyl-β-D-glucopyranoside. J Natl Cancer Inst 1982; 69: 131–6

    PubMed  CAS  Google Scholar 

  59. Kahan BD, Reisfeld RA. Transplantation antigen. Science 1969; 164: 514–21

    Article  PubMed  CAS  Google Scholar 

  60. Zimmerman CE, Bush GG, Stuart FP, et al. Canine renal homografts after pretreatment with subcellular splenic antigens. Surgery 1968; 63: 437–45

    PubMed  CAS  Google Scholar 

  61. Surh CD, Sprent J. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 1994; 372: 100–3

    Article  PubMed  CAS  Google Scholar 

  62. Markmann JF, Odorico JS, Bassiri H, et al. Deletion of donorreactive T lymphocytes in adult mice after intrathymic inoculation with lymphoid cells. Transplantation 1993; 55: 871–7

    Article  PubMed  CAS  Google Scholar 

  63. Oluwole SF, Jin MX, Chowdhury NC, et al. Effectiveness of intrathymic inoculation of soluble antigens in the induction of specific unresponsiveness to rat islet allografts without transient recipient immunosuppression. Transplantation 1994; 58: 1077–81

    PubMed  CAS  Google Scholar 

  64. Hamashima T, Stepkowski SM, Smith S, et al. Induction of transplantation tolerance by a single intrathymic injection of 3M KCl extracted donor histocompatibility antigens combined with two doses of anti-rat α/β T cell receptor monoclonal antibodies. Transplantation 1994; 58: 105–6

    PubMed  CAS  Google Scholar 

  65. Chowdhury NC, Jin MX, Hardy MA, et al. Donor-specific unresponsiveness to murine cardiac allografts induced by intrathymic soluble alloantigens is dependent on alternate pathway of antigen presentation. J Surg Res 1995; 59: 91–6

    Article  PubMed  CAS  Google Scholar 

  66. Ohajekwe OA, Chowdhury NC, Fiedor PS, et al. Transplantation tolerance to rat cardiac and islet allografts by posttransplant intrathymic inoculation of soluble alloantigens. Transplantation 1995; 60: 1139–43

    Article  PubMed  CAS  Google Scholar 

  67. Florence LS, Ito T, Ang K, et al. The synergistic effect of total lymphoid irradiation with extracted donor alloantigen to induce transplantation unresponsiveness. Transplantation 1989; 47: 156–62

    Article  PubMed  CAS  Google Scholar 

  68. Ito T, Stepkowski SM, Kahan BD. Soluble antigen and cyclo-sporine induced specific unresponsiveness in rats. Transplantation 1990; 49: 422–8

    Article  PubMed  CAS  Google Scholar 

  69. Pouteil-Noble C, Wood KJ, Morris PJ. The effect of purified class II major histocompatibility complex antigen on the survival of vascularized organ allografts in the rat. Transplantation 1993; 55: 656–8

    Article  PubMed  CAS  Google Scholar 

  70. Didlake R, Kim EK, Kahan BD. Ability of 3M KCl-extracted histocompatibility antigen to potentiate the immunosuppressive effect of cyclosporine to prolong the survival of heterotropic rat cardiac allografts. Transplantation 1988; 46: 743–7

    Article  PubMed  CAS  Google Scholar 

  71. Goto S, Stepkowski SM, Kahan BD. Benefit of multiple over single doses of 3M KCl-extracted histocompatibility antigen in the potentiating cyclosporine-induced prolongation of rat cardiac allograft survival. Transplantation 1992; 53: 705–7

    Article  PubMed  CAS  Google Scholar 

  72. Hamashima T, Stepkowski SM, Kahan BD. Synergistic effects of 3M KCl-extracted antigens with cyclosporine or cyclosporine/rapamycin to prolong heart allograft survival in rats. Transplant Proc 1994; 26: 3053–5

    PubMed  CAS  Google Scholar 

  73. Clayberger C, Parham P, Rothbard J, et al. HLA-A2 peptides can regulate cytolysis by human allogeneic T lymphocyte. Nature 1987; 330: 763–5

    Article  PubMed  CAS  Google Scholar 

  74. Parham P, Clayberger C, Zorn SL. Inhibition of alloreactive cytotoxic T lymphocytes by peptides from the α2 domain of HLA-A2. Nature 1987; 325: 625–8

    Article  PubMed  CAS  Google Scholar 

  75. Clayberger C, Lyu SC, Dekruyff R, et al. Peptides corresponding to the CD8 and CD4 binding domains of HLA molecules block T lymphocyte immune responses in vitro. J Immunol 1994; 53: 946–51

    Google Scholar 

  76. Salter RD, Benjamin RJ, Wesley PK, et al. Abinding site for the T cell co-receptor, CD8 on the alpha 3 domain of HLA-A2. Nature 1990; 345: 41–6

    Article  PubMed  CAS  Google Scholar 

  77. Benham AM, Fabre JW. Fine specificity of peptide determinants for indirect T cell recognition of class I MHC alloantigens. Transplantation 1994; 58: 1236–40

    PubMed  CAS  Google Scholar 

  78. Benham AM, Fabre JW. Elucidation of key peptide determinants involved in an indirect T cell allorecognition pathway of rat kidney allograft rejection. Transplant Proc 1995; 27: 547–8

    PubMed  CAS  Google Scholar 

  79. Benham AM, Sawyer GJ, Fabre JW. T and B cell responsiveness to donor class I MHC molecules and peptides in long survivors with kidney allografts. Transplantation 1996; 61: 1455–60

    Article  PubMed  CAS  Google Scholar 

  80. Krensky AM, Clayberger C. Immunomodulation by HLA class I-derived peptides. Transplant Proc 1996; 28: 3026–8

    PubMed  CAS  Google Scholar 

  81. Krensky AM, Clayberger C. Immunologic tolerance: tailored antigen. Transplant Proc 1996; 28: 2075–7

    PubMed  CAS  Google Scholar 

  82. Woo J, Gao L, Cornejo MC, et al. A synthetic dimeric HLA class I peptide inhibits T cell activity in vitro and prolongs allogeneic heart graft survival in a mouse model. Transplantation 1995; 60: 1156–63

    Article  PubMed  CAS  Google Scholar 

  83. Cuturi MC, Josien R, Douillard P, et al. Prolongation of allogeneic heart graft survival in rats by administration of a peptide from the α1 helix of the domain of HLA-B7 01. Transplantation 1995; 59: 661–9

    Article  PubMed  CAS  Google Scholar 

  84. Hanaway MJ, Geissler ED, Wang J, et al. Immunosuppressive effects of an HLA class I-derived peptide in a rat cardiac allograft model. Transplantation 1996; 61: 1222–8

    Article  PubMed  CAS  Google Scholar 

  85. Nisco S, Vriens P, Hoyt G, et al. Induction of allograft tolerance by an HLA class-I-derived peptide and cyclosporine A. J Immunol 1994; 152: 3786–92

    PubMed  CAS  Google Scholar 

  86. Buelow R, Veyron P, Clayberger C, et al. Prolongation of skin allograft survival in mice following administration of Al-lotrap. Transplantation 1995; 59: 455–60

    PubMed  CAS  Google Scholar 

  87. Pouletty P, Floc’h R, Buelow R, et al. In vivo effect of Allotrap in humans [abstract 125]. J Am Soc Nephrol 1994; 5: 987

    Google Scholar 

  88. Giral M, Cuturi M-C, Ngugen J-M, et al. Decreased cytotoxic activity of natural killer cells in kidney allograft recipients treated with human HLA-derived peptide. Transplantation 1997; 63: 1004–10

    Article  PubMed  CAS  Google Scholar 

  89. Colovai AI, Renna-Molajoni E, Cocciolo PL, et al. Suppression of allorecognition by use of synthetic peptides. Transplant Proc 1996; 28: 3029–31

    PubMed  CAS  Google Scholar 

  90. Murphy B, Akalin E, Watschinger B, et al. Inhibition of the alloimmune response with synthetic nonpolymorphic class II MHC peptides. Transplant Proc 1995; 27: 409

    PubMed  CAS  Google Scholar 

  91. Sayegh MH, Perico P, Imberti I, et al. Thymic recognition for class JJ MHC allopeptides induces donor specific unresponsiveness to renal allografts. Transplantation 1993; 56: 461–5

    Article  PubMed  CAS  Google Scholar 

  92. Hancock WW, Khoury SJ, Carpenter CB, et al. Differential effects of oral versus intrathymic administration of polymorphic MHC class II peptides on mononuclear and endothelial cell activation and cytokine expression during a delayed type hypersensitivity response. Am J Pathol 1994; 144: 1149–58

    PubMed  CAS  Google Scholar 

  93. Sayegh MH, Perico N, Gallon L, et al. Mechanisms of acquired thymic unresponsiveness to renal allografts: thymic recognition of immunodominant allo-MHC peptides induces peripheral T cell anergy. Transplantation 1994; 58: 125–32

    PubMed  CAS  Google Scholar 

  94. Sayegh MH, Khoury SK, Hancock WW, et al. Induction of immunity and oral tolerance with polymorphic class II MHC allopeptides in the rat. Proc Natl Acad sci USA 1992; 89: 7762–6

    Article  PubMed  CAS  Google Scholar 

  95. Noessner E, Golgberg JE, Naftzger C, et al. HLA-derived peptides which inhibit T cell function bind to members of the heat-shock protein 70 family. J Exp Med 1996; 183: 339–48

    Article  CAS  Google Scholar 

  96. Fan QOR, Garboczi DN, Winter CC, et al. Direct binding of a soluble natural killer cell inhibitory receptor to a soluble human leukocyte antigen-Cw4 class I major histocompatibility complex molecule. Proc Natl Acad sci USA 1996; 93: 7178–83

    Article  PubMed  CAS  Google Scholar 

  97. Lanier LL. The role of natural killer cells in transplantation. Curr Opin Immunol 1995; 7: 626–31

    Article  PubMed  CAS  Google Scholar 

  98. Vignali DAA, Strominger JL. Amino acid residues that flank core peptide epitopes and extracellular domains of CD4 modulate differential signaling through the T cell receptor. J Exp Med 1994; 179: 1945–56

    Article  PubMed  CAS  Google Scholar 

  99. Monji T, Pious D. Exogenously provided peptides fail to complex with intracellular class II molecules for presentation by antigen-presenting cells. J Immunol 1997; 158: 3155–64

    PubMed  CAS  Google Scholar 

  100. Horton RM, Cai Z, Ho SN, et al. Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction. Biotechniques 1990; 8: 528–35

    PubMed  CAS  Google Scholar 

  101. Qian S, Li FY, Lu L, et al. Presensitization by skin grafting from major histocompatibility complex class I or major histocompatibility complex class II deficient mice identifies class I antigens as inducers of allosensitization. Immunology 1995; 85: 82–7

    PubMed  CAS  Google Scholar 

  102. Guttmann RD, Forbes DC, Cramer DV, et al. Cardiac allograft rejection and enhancement in natural recombinant rat strains. Transplantation 1980; 30: 216–8

    Article  PubMed  CAS  Google Scholar 

  103. Gracie JA, Bolton EM, Porteous C, et al. T cell requirements for the rejection of renal allografts bearing an isolated class I MHC disparity. J Exp Med 1990; 172: 1547–57

    Article  PubMed  CAS  Google Scholar 

  104. Halloran PF, Schlaut J, Solez K, et al. The significance of the anti-class I response. Transplantation 1992; 53: 550–5

    Article  PubMed  CAS  Google Scholar 

  105. Cuturi MC, Josien R, Cantarovich D, et al. Decreased anti-donor major histocompatibility complex class I and increased class II alloantibody response in allograft tolerance in adult rats. Eur J Immunol 1994; 24: 1627–31

    Article  PubMed  CAS  Google Scholar 

  106. Rada C, Lorenzi R, Powis SJ, et al. Concerted evolution of class I genes in the major histocompatibility complex of murine rodents. Proc Natl Acad sci USA 1990; 87: 2167

    Article  PubMed  CAS  Google Scholar 

  107. Wang M, Stepkowski SM, Tian L, et al. Nucleotide sequences of three distinct clones coding for rat heavy chain class I major histocompatibility antigens. Immunogenetics 1996; 43: 318–20

    Article  PubMed  CAS  Google Scholar 

  108. Salgar SK, Sawai H, Kunz HW, et al. Cloning and expression of the rat class I MHC gene RT1.A1. Immunogenetics 1994; 39: 447

    Article  PubMed  CAS  Google Scholar 

  109. Wang M, Stepkowski SM, Hebert JS, et al. Nucleotide sequences of three H-2K and three H-2D complementary DNA clones coding mouse class I MHC heavy chain proteins. Ann Transplant 1996; 1: 26–31

    PubMed  CAS  Google Scholar 

  110. Ghobrial RR, Hamashima T, Kloc M, et al. Membrane-bound or soluble truncated RTl.Aa rat class I major histocompatibility antigens induce specific alloimmunity. Transplantation 1995; 60: 602–10

    Article  PubMed  CAS  Google Scholar 

  111. Ghobrial RR, Hamashima T, Wang ME, et al. Induction of transplantation tolerance by chimeric donor/recipient class I RTl.Aa molecules. Transplantation 1996; 62: 1002–10

    Article  PubMed  CAS  Google Scholar 

  112. Wang M, Stepkowski SM, Wang M, et al. Induction of specific allograft immunity by soluble class I MHC heavy chain protein produced in a baculovirus expression system. Transplantation 1996; 61: 448–57

    Article  PubMed  CAS  Google Scholar 

  113. Wang M, Stepkowski SM, Yu J, et al. Localization of cryptic tolerogenic epitopes in the α1 helical region of the RT1.AU alloantigen. Transplantation 1997; 63: 1373–9

    Article  PubMed  CAS  Google Scholar 

  114. Suzuki S, Enosawa S, Kakefuda T, et al. A novel immunosuppressant, FTY720, with a unique mechanism of action, induces long-term graft acceptance in rat and dog allotrans-plantation. Transplantation 1996; 61: 200–5

    Article  PubMed  CAS  Google Scholar 

  115. Chiba K, Hoshino Y, Suzuki C, et al. FTY720, a novel immunosuppressant possessing unique mechanisms. I. Prolongation of skin allograft survival and synergistic effect in combination with cyclosporine in rats. Transplant Proc 1996; 28: 1056–9

    PubMed  CAS  Google Scholar 

  116. Hoshino Y, Suzuki C, Ohtsuki M, et al. FTY720, a novel immunosuppressant possessing unique mechanisms. II. Long-term graft survival induction in rat heterotopic cardiac allografts and synergistic effect in combination with cyclosporine A. Transplant Proc 1996; 28: 1060–1

    PubMed  CAS  Google Scholar 

  117. Masubuchi Y, Kawaguchi T, Ohtsuki M, et al. FTY720, a novel immunosuppressant possessing unique mechanisms. IV. Prevention of graft versus host reactions in rats. Transplant Proc 1996; 28: 1064–5

    PubMed  CAS  Google Scholar 

  118. Stepkowski SM, Tu Y, Condon TP, et al. Blocking of heart allograft rejection by intercellular adhesion molecule-1 antisense oligonucleotides alone or in combination with other immunosuppressive modalities. J Immunol 1994; 153: 5336–46

    PubMed  CAS  Google Scholar 

  119. Liu Z, Williams KP, Chang YH, et al. Immunodominance: a single amino acid substitution without an antigenic site alters intramolecular selection of T cell determinants. J Immunol 1993; 151: 1852–8

    PubMed  CAS  Google Scholar 

  120. Sloan-Lancaster J, Evavold BD, Allen PM. Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen presenting cells. Nature 1993; 363: 156–9

    Article  PubMed  CAS  Google Scholar 

  121. Janeway CAJ, Dianzani U, Portoles P, et al. Cross-linking and conformational change in T cell receptor: role in activation and in repertoire selection. Cold Spring Harb Symp Quant Biol 1989; 54: 657–66

    Article  PubMed  CAS  Google Scholar 

  122. Sloan-Lancaster J, Shaw AS, Rothbard JB, et al. Partial T cell signaling: altered phospho-zeta and lack of ZAP70 recruitment in APL-induced T cell anergy. Cell 1994; 79: 913–22

    Article  PubMed  CAS  Google Scholar 

  123. Rodey GE, Neylan JF, Whelchel JD, et al. Epitope specificity of HLA class I alloantibodies. I. Frequency analysis of antibodies to private versus public specificities in potential transplant recipients. Human Immunol 1994; 39: 272–80

    Article  CAS  Google Scholar 

  124. Doxiadis II, Smits JMA, Schreuder GMT, et al. Association between specific HLA combinations and probability of kidney graft loss: the taboo concept. Lancet 1996; 348: 850–3

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Immunology and Organ Transplantation, Department of Surgery, University of Texas - Houston Medical School, 6431 Fannin, Suite 6.240, Houston, Texas, TX 77030, USA

    Shih-Chieh Chueh &  Barry D. Kahan

Authors
  1. Shih-Chieh Chueh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barry D. Kahan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barry D. Kahan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chueh, SC., Kahan, B.D. Altered Major Histocompatibility Complex Proteins and Peptides for the Induction of Tolerance After Organ Transplantation. BioDrugs 9, 397–417 (1998). https://doi.org/10.2165/00063030-199809050-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-199809050-00005

Keywords

Search

Navigation