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Gene Technology pp 381–396Cite as

Transplantation Immunology: Peptides in the groove cause histocompatibility

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Part of the book series: NATO ASI Series ((ASIH,volume 94))

Summary

Organ and bone marrow transplantation is frequently complicated by immune responses against major and minor histocompatibility antigens. This article will discuss current concepts of the molecular nature of histocompatibility antigens. The functional units that trigger immune responses by T lymphocytes are peptides bound to the peptide binding groove of major histocompatibility complex (MHC) class I and class II molecules. In MHC mismatched transplant situations, T lymphocytes recognise donor MHC molecules displaying donor derived peptides. In MHC matched transplant situations, T cell immunity is directed against donor-specific peptides bound to the groove of MHC molecules. These donor-specific peptides are derived from polymorphic cellular proteins, named minor histocompatibility (mH) antigens. We propose that immune responses against mismatched MHC antigens and mH antigens are probably directed against a small number of immunodominant peptides. In future, it may become possible to exploit such peptides for tolerance induction, which may lead to specific downregulation of unwanted T cell responses in organ and bone marrow transplantation.

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References

  • Aichele, P., Kyburz, D., Ohashi, P.S., Odermatt, B., Zinkernagel, R.M., Hengartner, H. and Pircher, H. (1994) Pep tide-induced T-cell tolerance to prevent autoimmune diabetes in a transgenic mouse model. Proc Natl Acad Sci USA 91: 444–8

    Article  PubMed  CAS  Google Scholar 

  • Amigorena, S., Drake, J.R., Webster, P. and Mellman, I. (1994) Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes [see comments]. Nature. 369: 113–20

    Article  PubMed  CAS  Google Scholar 

  • Aosai, F., Ohlen, C., Ljunggren, H.G., Hoglund, P., Franksson, L., Ploegh, H., Townsend, A., Karre, K. and Stauss, H.J. (1991) Different types of allospecific CTL clones identified by their ability to recognize peptide loading-defective target cells. Eur J Immunol. 21: 2767–74

    Article  PubMed  CAS  Google Scholar 

  • Auchincloss, H.J., Lee, R., Shea, S., Markowitz, J.S., Grusby, M.J. and Glimcher, L.H. (1993) The role of “indirect” recognition in initiating rejection of skin grafts from major histocompatibility complex class IIdeficient mice. Proc Natl Acad Sci USA. 90: 3373–7

    Article  PubMed  CAS  Google Scholar 

  • Bailey, D. and Mobraaten, L. (1969)Estimates of the number of loci contributing to the histoincompatiibility between C57BL/6 and BALB/c strains of mice. 7:394–400

    CAS  Google Scholar 

  • Barnd, D.L., Lan, M.S., Metzgar, R.S. and Finn, O.J. (1989) Specific, major histocompatibility complex-unrestricted recognition of tumor-associated mucins by human cytotoxic T cells. Proc Natl Acad Sci USA. 86: 7159–63

    Article  PubMed  CAS  Google Scholar 

  • Bevan, M.J. (1984) Immunol. Today. 5: 128.

    Google Scholar 

  • Bjorkman, P.J., Saper, M.A., Samraoui, B., Bennett, W.S., Strominger, J.L. and Wiley, D.C. (1987a) The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 329: 512–8

    Article  PubMed  CAS  Google Scholar 

  • Bjorkman, P.J., Saper, M.A., Samraoui, B., Bennett, W.S., Strominger, J.L. and Wiley, D.C. (1987b) Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 329: 506–12

    Article  CAS  Google Scholar 

  • Brown, J.H., Jardetzky, T.S., Gorga, J.C., Stern, L.J., Urban, R.G., Strominger, J.L. and Wiley, D.C. (1993) Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1 [see comments]. Nature. 364: 33–9

    Article  PubMed  CAS  Google Scholar 

  • Choi, Y.W., Herman, A., Digiusto, D., Wade, T., Marrack, P. and Kappler, J. (1990) Residues of the variable region of the T-cell-receptor beta-chain that interact with S. aureus toxin superantigens. Nature. 346: 471–3

    Article  PubMed  CAS  Google Scholar 

  • Clayberger, C., Lyu, S.C., Dekruyff, R., Parham, P. and Krensky, A.M. (1994) Peptides corresponding to the CD8 and CD4 binding domains of HLA molecules block T lymphocyte immune responses in vitro. J Immunol. 153: 946–51

    PubMed  CAS  Google Scholar 

  • Connolly, J.M. (1994) The peptide p2Ca is immunodominant in allorecognition of Ld by (J-chain Vp8+ but not Vp8 strains. Proc. Natl. Acad. Sci. 91: 11482–486

    Article  PubMed  CAS  Google Scholar 

  • Deverson, E.V., Gow, I.R., Coadwell, W.J., Monaco, J.J., Butcher, G.W. and Howard, J.C. (1990) MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters [see comments]. Nature. 348: 738–41

    Article  PubMed  CAS  Google Scholar 

  • Friedman, A. and Weiner, H.L. (1994) Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proc Natl Acad Sci USA. 91: 6688–92

    Article  PubMed  CAS  Google Scholar 

  • Graff, R. and Bailey, D. (1973) The non-H-2 histocompatibility loci and their antigens. Transplant Rev. 15: 26–49

    PubMed  CAS  Google Scholar 

  • Graff, R., Hildemann, W. and Snell, G. (1966) Histocompatibility genes of mice. VI. allografts in mice congenic at various non-H-2 histocompatibility loci. 4: 425–437

    CAS  Google Scholar 

  • Heath, W.R., Hurd, M.E., Carbone, F.R. and Sherman, L.A. (1989) Peptidedependent recognition of H-2Kbby alloreactive cytotoxic T lymphocytes. Nature. 341: 749–752

    Article  PubMed  CAS  Google Scholar 

  • Henderson, R.A., Cox, A.L., Sakaguchi, K., Appella, E., Shabanowitz, J., Hunt, D.F. and Engelhard, V.H. (1993) Direct identification of an endogenous peptide recognized by multiple HLA-A2.1-specific cytotoxic T cells. PNAS. 90: 10275–10279

    Article  PubMed  CAS  Google Scholar 

  • Hunt, D.F., Henderson, R.A., Shabanowitz, J., Sakaguchi, K., Michel, H., Sevilir, N., Cox, A.L., Appella, E. and Engelhard, V.H. (1992) Characterization of peptides bound to class I MHC Molecule HLA-A2.1 by mass spectrophotometry. Science. 255: 1261–1263

    Article  PubMed  CAS  Google Scholar 

  • Jerome, K.R., Barnd, D.L., Bendt, K.M., Boyer, C.M., Taylor, P.J., McKenzie, I.F., Bast, R.J. and Finn, O.J. (1991) Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells. Cancer Res. 51: 2908–16

    PubMed  CAS  Google Scholar 

  • Karp, D.R. and Long, E.O. (1992) Identification of HLA-DRip chain residues critical for binding staphylococcal enterotoxins A and E.J Exp Med. 175: 415–424

    Article  PubMed  CAS  Google Scholar 

  • Krensky, A.M. and Clayberger, C. (1994) The induction of tolerance to alloantigens using HLA-based synthetic peptides. Curr. Opin. Immunol. 6:791–796

    Article  PubMed  CAS  Google Scholar 

  • Langlade-Demoyen, P, Levraud, J.P, Kourilisky, P, and Abastado, J.P,(1994) Primary cytotoxic T lymphocyte induction using peptidestripped autologous cells. Intern. Immunol. 6: 1759–66

    Article  CAS  Google Scholar 

  • Lee, R.S., Grusby, M.J., Glimcher, L.H., Winn, H.J. and Auchincloss, H.J. (1994) Indirect recognition by helper cells can induce donor-specific cytotoxic T lymphocytes in vivo. J Exp Med. 179: 865–72

    Article  PubMed  CAS  Google Scholar 

  • Loveland, B., Wang, C.R., Yonekawa, H., Hermel, E. and Lindahl, K.F. (1990) Maternally transmitted histocompatibility antigen of mice: a hydrophobic peptide of a mitochondrially encoded protein. Cell. 60:971–80

    Article  PubMed  CAS  Google Scholar 

  • Matzinger, P. and Bevan, M.J. (1977) Cell. Immunol. 29: 1

    Article  PubMed  CAS  Google Scholar 

  • Monaco, J.J. (1992) A molecular model of MHC class-I-restricted antigen processing. Immunol Today. 13: 173–9

    Article  PubMed  CAS  Google Scholar 

  • Monaco, J.J., Cho, S. and Attaya, M. (1990) Transport protein genes in the murine MHC: possible implications for antigen processing. Science. 250: 1723–6

    Article  PubMed  CAS  Google Scholar 

  • Nisco, S., Vriens, P., Hoyt, G., Lyu, S.C., Farfan, F., Pouletty, P., Krensky, A.M. and Clayberger, C. (1994) Induction of allograft tolerance in rats by an HLA class-I-derived peptide and cyclosporine A. J Immunol 152: 3786–92

    PubMed  CAS  Google Scholar 

  • Perham, P., Clayberger, C., Zorn, S.L., Ludwig, D.S., Schoolnik, G.K. and Krensky, A.M. (1987) Inhibition of alloreactive cytotoxic T lymphocytes by peptides from the al domain of HLA-A2. Nature. 325: 625–628

    Article  Google Scholar 

  • Roopenian, D.C. (1992) What are minor histocompatibility loci? A new look at an old question. Immunol Today. 13:7–10

    Article  PubMed  CAS  Google Scholar 

  • Rotzschke, O., Falk, K., Faath, S. and Rammensee, H.G. (1991) On the nature of peptides involved in T cell alloreactivity. J Exp Med. 174: 1059–71

    Article  PubMed  CAS  Google Scholar 

  • Salter, R.D., Norment, A.M., Chen, B.P., Clayberger, C., Krensky, A.M., Littman, D.R. and Parham, P. (1989) Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature. 338:345–7

    Article  PubMed  CAS  Google Scholar 

  • Sanderson, F., Kleijmeer, M.J., Kelly, A., Verwoerd, D., Tulp, A., Neefjes, J.J., Geuze, H.J. and Trwsdale, J. (1994) Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments. Science. 266: 1566–1569

    Article  PubMed  CAS  Google Scholar 

  • Sayegh, M.H., Khoury, S.J., Hancock, W.W., Weiner, H.L. and Carpenter, C.B. (1992) Induction of immunity and oral tolerance with polymorphic class II major histocompatibility complex allopeptides in the rat. Proc Natl Acad Sci USA. 89: 7762–6

    Article  PubMed  CAS  Google Scholar 

  • Sercarz, E.E., Lehmann, P.V., Ametani, A., Benichou, G., Miller, A. and Moudgil, K. (1993) Dominance and crypticity of T cell antigenic determinants. Annu Rev Immunol. 11: 729–66

    Article  PubMed  CAS  Google Scholar 

  • Speiser, D.E., Zurcher, T., Ramseier, H., Hengartner, H., Staeheli, P., Haller, O. and Zinkernagel, R.M. (1990) Nuclear myxovirus-resistance protein Mx is a minor histocompatibility antigen. Proc Natl Acad Sci USA. 87:2021–5

    Article  PubMed  CAS  Google Scholar 

  • Sun, J.B., Holmgren, J. and Czerkinsky, C. (1994) Cholera toxin B subunit: An efficient transmucosal carrier-delivery system for induction of perigheral immunological tolerance. Proc. Natl. Acad. Sci. USA. 91: 10795–799

    Article  PubMed  CAS  Google Scholar 

  • Topalian, S.L., Rivoltini, L., Mancini, M., Markus, N.R., Robbins, P.F., Kawakami, Y. and Rosenberg, S.A. (1994) Human CD4+ T cells specifically recognise a shared melanoma-associated antigen encoded by the tyrosinase gene. Proc. Natl. Acad. Sci. USA. 91: 9461–9465

    Article  PubMed  CAS  Google Scholar 

  • Trowsdale, J., Hanson, I., Mockridge, I., Beck, S., Townsend, A. and Kelly, A. (1990) Sequences encoded in the class II region of the MHC related to the ’ABC’ superfamily of transporters [see comments]. Nature. 348:741–4

    Article  PubMed  CAS  Google Scholar 

  • Udaka, K., Tsomides, T.J. and Eisen, H.N. (1992) A naturally occurring peptide recognized by alloreactive CD8+ cytotoxic T lymphocytes in association with a class I MHC protein. Cell. 69:989–98

    Article  PubMed  CAS  Google Scholar 

  • Weiner, H.L., Friedman, A., Miller, A., Khoury, S.J.,Santos, L., Sayegh, M., Nussenblatt, R.B., Trentham, D.E. and Hafler, D.A. (1994) Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu Rev Immunol 12: 809–37

    Article  PubMed  CAS  Google Scholar 

  • Wettstein, P.J. (1986) Immunodominance in the T-cell response to multiple non-H-2 histocompatibility antigens. II. Observation of a hierarchy among dominant antigens. Immunogenetics. 24: 24–31

    CAS  Google Scholar 

  • Yin, L., Poirier, G., Neth, O., Hsuan, J.J., Totty, N.F. and Stauss, H.J. (1993) Few peptides dominate CTL responses to single and multiple minor histocompatibility antigens. Int. Immunol 5:1003–1009

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Imperial Cancer Research Fund, Tumour Immunology, Unit, 91 Riding House Street, London, WC1 8BT, UK

    H. J. Stauss, C. Thomas, P. Nathan, E. Sadovnikova, O. Neth & L. Yin

Authors
  1. H. J. Stauss
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  2. C. Thomas
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  3. P. Nathan
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  4. E. Sadovnikova
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  5. O. Neth
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  6. L. Yin
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Editors and Affiliations

  1. Universitätskrankenhaus Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany

    Axel R. Zander

  2. Heinrich-Pette-lnstitut für Experimentelle Virologie und Immunologie, Universität Hamburg, Martinistraße 52, D-20246, Hamburg, Germany

    Wolfram Ostertag

  3. City Center for Advanced Medical Technologies, Bone Marrow Transplantation Center, Pr. Dynamo 3, 197042, St.Petersburg, Russia

    Boris V. Afanasiev

  4. Laboratory for Gene Structure Expression, Medical Research Council Institute, The Ridgeway, Mill Hill, London, NW71AA, UK

    Frank Grosveld

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© 1996 Springer-Verlag Berlin Heidelberg

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Stauss, H.J., Thomas, C., Nathan, P., Sadovnikova, E., Neth, O., Yin, L. (1996). Transplantation Immunology: Peptides in the groove cause histocompatibility. In: Zander, A.R., Ostertag, W., Afanasiev, B.V., Grosveld, F. (eds) Gene Technology. NATO ASI Series, vol 94. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61122-3_28

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  • DOI: https://doi.org/10.1007/978-3-642-61122-3_28

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  • Print ISBN: 978-3-642-64704-8

  • Online ISBN: 978-3-642-61122-3

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