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The self and the nonself: Immunorecognition and immunologic functions

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Abstract

For almost a century self-nonself discrimination has been considered the driving force of the immune system and the dogma of self-tolerance (horror autotoxicus) the essential issue for understanding protective immunity and pathologic autoreactivity. This classical picture has been recently challenged by the discovery that the immune system is influenced by internal activation (amor autocognitus) and autoreactive clones are both present and activated in healthy individuals. Central to the concepts of reactivity and tolerance, in other terms, to physiology and pathology, is the analysis of structures involved in immunorecognition and as they contribute to the outcome of the immune response. The capacity of the immune system to recognize nonself structures and eventually react to them developed during evolution probably before the generation of clonally distributed antigen receptors. The high level of autoreactivity that characterizes the immune system seems to suggest that immunocompetent cells never learned to ignore the self, but rather that, sometime during evolution, they specialized in the function of self-identification, one of the most basic activities of all living cells. Autoimmune diseases would result from a pathologic deviation of a physiologic function, just as many other diseases do.

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References

  1. Kappler JW, Roehn N, Marrack P: T cell tolerance by clonal elimination in the thymus. Cell 1987;49:273.

    Article  PubMed  CAS  Google Scholar 

  2. Fowlkes BJ, Schwartz RH, Pardoll DM: Deletion of self-reactive thymocytes occurs at a CD4+8+ precursor stage. Nature 1988;334:620.

    Article  PubMed  CAS  Google Scholar 

  3. Kisielow P, Buthmann H, Staerz UD, Steinmetz M, von Boehmer H: Tolerance in T cell receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature 1988;333:743.

    Article  Google Scholar 

  4. Hengartner H, Odermatt B, Schneider R, et al: Deletion of selfreactive T cells before entry into the thymus medulla. Nature 1988;336:388.

    Article  PubMed  CAS  Google Scholar 

  5. Lamb JR, Skidmore BJ, Green N, Chiller JM, Feldmann M: Induction of tolerance in influence virus-immune T lymphocyte clones with syngeneic peptides of influence hemagglutinin. J Exp Med 1983;157:1434.

    Article  PubMed  CAS  Google Scholar 

  6. Schartz RH: A cell culture model for T lymphocyte clonal anergy. Nature 1990;248:1349.

    Google Scholar 

  7. Gaur A, Wiers B, Liu A: Amelioration of autoimmune encephalomyelitis by myelin basic protein synthetic peptide-induced anergy. Science 1992;258:1491.

    Article  PubMed  CAS  Google Scholar 

  8. Celis E, Saibara T: Binding of T cell receptor to major histocompatibility complex class II-peptide complexes at the single-cell level results in the induction of antigen unrespensiveness (anergy). Eur J Immunol 1992; 22:3127.

    Article  PubMed  CAS  Google Scholar 

  9. Lo D: T-cell tolerance. Curr Opin Immunol 1992;4:711.

    Article  PubMed  CAS  Google Scholar 

  10. Boitard C, Yasunami R, Dardenne M, Bach JF: T cell mediated inhibition of the transfer of autoimmune diabetes in NOD mice. J Exp Med 1983;169:1669.

    Article  Google Scholar 

  11. Ellerman KE, Powers JM, Brostoff SW: A suppressor T lymphocytes line for autoimmune encephalomyelitis. Nature 1988;331:265.

    Article  PubMed  CAS  Google Scholar 

  12. Bloom BR, Salgame P, Diamond B: Revisiting and revising suppressor T cells. Immunol Today 1992;13:131.

    Article  PubMed  CAS  Google Scholar 

  13. Wang SH, Chen G, Zhang K: Effects of thymosin and insulin on suppressor T cell in type 1 diabetes. Diabetes Res 1992;19:21.

    PubMed  CAS  Google Scholar 

  14. Dresser DW: Most IgM-producing cells in the mouse secrete autoantibodies (rheumatoid factor). Nature 1978;274:480.

    Article  PubMed  CAS  Google Scholar 

  15. Guilbert B, Dighiero G, Avrameas S: Naturally occurring antibodies against nine common antigens in normal humans. I. Detection, isolation and characterization. J Immunol 1982;128:2779.

    PubMed  CAS  Google Scholar 

  16. Dighiero G, Guilbert B, Avrameas S: Naturally occurring antibodies against nine common antigens in normal humans. II. High incidence of monoclonal Ig exhibiting antibody activity against actin and tubulin and sharing antibody specificity with natural antibody. J Immunol 1982;128:2788.

    PubMed  CAS  Google Scholar 

  17. Dighiero G, Lymberi JC, Mazie S, et al: Murine hybridomas secreting natural monoclonal antibodies reacting with self antigens. J Immunol 1983;131:2267.

    PubMed  CAS  Google Scholar 

  18. Dighiero G, Lymberi P, Holmberg D, Lundquist I, Coutihno A, Avrameas S: High frequency of natural antibodies in normal newborn mice. J Immunol 1985;134:765.

    PubMed  CAS  Google Scholar 

  19. Prabhakar BS, Saegusa J, Onodera T, Notkins AL: Lymphocytes capable of making monoclonal autoantibodies that react with multiple organs are a common feature of the normal B cell repertoire. J Immunol 1984;133:2815.

    PubMed  CAS  Google Scholar 

  20. Coutihno A, Forni L, Holmberg D, Ivars F, Vaz N: From an antigen-centered, clonal perspective of immune responses to an organism-centered, network perspective of autonomous activity in a self-referential immune system. Immunol Rev 1984;79:151.

    Article  Google Scholar 

  21. Hoojkaas H, Benner R, Pleasants JR, Wostman BS: Isotypes and specificities of immunoglobulins produced by germ-free mice fed chemically defined ultrafiltered ‘antigenfrec’ diet. Eur J Immunol 1984;14:1127.

    Article  Google Scholar 

  22. Huetz F, Jacquemart F, Pena Rossi C, Varela F, Coutihno A: Autoimmunity: The moving boundaries between physiology and pathology, in Bach JF (ed). Immunointervention in Autoimmune Diseases. London, Academic Press, 1989, p11.

    Google Scholar 

  23. Berneman A, Ternynk T, Avrameas S: Natural mouse IgG reacts with self antigens including molecules involved in the immune response. Eur J Immunol 1992;22:625.

    Article  PubMed  CAS  Google Scholar 

  24. Del Guercio P, Marcelletti JF, Katz DH: B-cell lymphokines and activation of the immune system by internal structures. Immunol Today 1986;7:97.

    Google Scholar 

  25. Sinclair NRS, del Guercio P: Self-nonself discrimination: From ‘horror autoxicus’ to ‘amor autocognitus’. Submitted.

  26. Avrameas S: Natural autoreactive B cells and autoantibodies: The ‘know thyseif’ of the immune system. Ann Inst Pasteur 1986;137D:150.

    Google Scholar 

  27. Alt FW, Blackwell TK, Yancopoulos GD: Development of the primary antibody repertoire. Science 1987: 238:1079.

    Article  PubMed  CAS  Google Scholar 

  28. Marrack P, Kappler J: The T cell receptor. Science 1987;238:107.

    Article  Google Scholar 

  29. Davis MM, Bjorkman PJ: T-cell antigen receptor genes and T-cell recognition. Nature 1988;334:395.

    Article  PubMed  CAS  Google Scholar 

  30. Bierer B, Burakoff SG: T-lymphocyte activation: The biology and function of CD2 and CD4. Immunol Rev 1989;111:267.

    Article  PubMed  CAS  Google Scholar 

  31. Rudd CE, Anderson P, Morimoto C, Streuli M, Schlossman S: Molecular interactions, T-cell subsets and a role of the CD4/CD8:p56lck complex in human T-cell activation. Immunol Rev 1989;111:225.

    Article  PubMed  CAS  Google Scholar 

  32. Schraven B, Samstag Y, Altevogt P, Meurer SC: Association of CD2 and CD45 on human T lymphocytes. Nature 1990;345:71.

    Article  PubMed  CAS  Google Scholar 

  33. Berek A, Milstein C: The dynamic nature of the antibody repertoire. Immunol Rev 1988;105:5.

    Article  PubMed  CAS  Google Scholar 

  34. Hodes RJ: T-cell mediated regulation: Helps and suppression; in Paul WP (ed), Fundamental Immunology. New York, Raven Press, 1989, p 587.

    Google Scholar 

  35. Unanue ER: Macrophages, antigen-presenting cells, and the phenomenon of antigen handling and presentation, in Paul WP (ed): Fundamental Immunology, New York, Raven Press, 1989, p 95.

    Google Scholar 

  36. Brodsky FM, Guagliardi LE: The cell biology of antigen processing and presentation. Annu Rev Immunol 1991;9:707.

    Article  PubMed  CAS  Google Scholar 

  37. Braciale TJ, Braciale VL: Viral antigen presentation and MHC assembly. Semin Immunol 1992;4:81.

    PubMed  CAS  Google Scholar 

  38. Braciale TJ, Braciale VL: Antigen presentation: Structural themes and functional variations. Immunol Today 1991;12:124.

    Article  PubMed  CAS  Google Scholar 

  39. Monaco JJ: A molecular model of MHC class I-restricted antigen processing. Immunol Today 1992;13:173.

    Article  PubMed  CAS  Google Scholar 

  40. Todd JA, Acha-Orbea H, Bell JI, et al: A molecular basis for MHC class-II associated autoimmunity. Science 1988;240:1003.

    Article  PubMed  CAS  Google Scholar 

  41. Hill AVS, Elvin J, Willis C, et al: Molecular analysis of the association of HLA-B53 and resistance to malaria. Nature 1992;360:434.

    Article  PubMed  CAS  Google Scholar 

  42. Del Guercio P: Susceptibility to diabetes and the major histocompatibility complex: The 57th residue affair. Diabetic Med 1992;9:330.

    PubMed  Google Scholar 

  43. Christadoss P, Lennon VA, David C: Genetic control of proliferative response to acetylcholine receptor is under H2-linked Ir gene control. J Immunol 1979;123:2540.

    PubMed  CAS  Google Scholar 

  44. Fritz RB, Skeen MJ, Chou C-HJ, Garcia M, Egorov IK: Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. J Immunol 1985;134:2328.

    PubMed  CAS  Google Scholar 

  45. Del Guercio P, Leuchars E: The immune response in mice to the haptenic determinant DNP coupled to a thymus-independent carrier (levan). J Immunol 1972;109:951.

    PubMed  Google Scholar 

  46. Del Guercio P: Effect of adjuvant on the antibody response to a hapten on a thymus-independent carrier. Nature 1972;238:231.

    Google Scholar 

  47. Murray JS, Pfeiffer C, Madri J, Bottomly K: MHC control of CD4 T cell subset activation. II. A single peptide induces either humoral or cell-mediated responses in mice in distinct MHC genotype. Eur J Immunol 1992;22:559.

    Article  PubMed  CAS  Google Scholar 

  48. Murray JS, Madri J, Tite J, Carding SR, Bottomly K: MHC control of CD4+ T cell subset activation. J Exp Med 1989;170:2135.

    Article  PubMed  CAS  Google Scholar 

  49. Vitiello A, Potter TA, Sherman LA: The role of b2-microglobulin in peptide binding by class I molecules. Science 1990;250:1423.

    Article  PubMed  CAS  Google Scholar 

  50. Kelly A, Powis SH, Glynne R, Radley E, Beck S, Trowsdale J: Second proteasome-related gene in the human MHC class II region. Nature 1991;353:667.

    Article  PubMed  CAS  Google Scholar 

  51. Brown MG, Driscoll J, Monaco JJ: Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexes. Nature 1991;353:355.

    Article  PubMed  CAS  Google Scholar 

  52. Glynne R, Powis SH, Beck S, Kelly A, Kerr L-A, Trowsdale J: A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC. Nature 1991;353:357.

    Article  PubMed  CAS  Google Scholar 

  53. Oritz-Navarrete V, Seelig A, Gernold M, Frentzel S, Kloetzel PM, Hammerling GJ: Subunit of the ‘20S’ proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex. Nature 1991;353:662.

    Article  Google Scholar 

  54. Martinez CK, Monaco JJ: Homology of proteosome subunits to a major histocompatibility complex-linked gene. Nature 1991;353:664.

    Article  PubMed  CAS  Google Scholar 

  55. Barinaga M: Immune mystery revealed: How MHC meets antigen. Science 1990;250:1657.

    Article  PubMed  CAS  Google Scholar 

  56. Monaco JJ, Cho S, Attaya M: Transport protein genes in the murine MHC: Possible implications for antigen processing. Science 1990;250:1723.

    Article  PubMed  CAS  Google Scholar 

  57. Deverson EV, Gow IR, Coadwell WJ, Monaco JJ, Butcher GW, Howard JC: MHC class II region of the MHC related to the multidrug resistance family of transmembrane transporters. Nature 1990;348:738.

    Article  PubMed  CAS  Google Scholar 

  58. Trowsdale J, Hanson I, Mockridge I, Beck S, Towsend A: Sequences encoded in the class II region of the MHC related to the ‘ABC’ superfamily of transporters. Nature 1990;348:741.

    Article  PubMed  CAS  Google Scholar 

  59. Spies T, Bresnahan M, Bahram S, et al: A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature 1990; 348:744.

    Article  PubMed  CAS  Google Scholar 

  60. Colonna M, Bresnahan M, Bahram S, Strominger JL, Spies T: Allelic variants of the human putative transporter involved in antigen processing. Proc Natl Acad Sci USA 1992;89:3932.

    Article  PubMed  CAS  Google Scholar 

  61. Burnet FM, Fenner F: The Production of Antibodies. London, Mac-Millan, 1949.

    Google Scholar 

  62. Fiscer Lindahl K, Wilson DB: Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors. J Exp Med 1977; 145:508.

    Article  Google Scholar 

  63. Lafferty KH, Jones MAS: Reactions of the graft versus host (GVH) type. Aust J Exp Biol Med Sci 1969;47:17.

    Article  PubMed  CAS  Google Scholar 

  64. Asantila T, Vahala J, Toivanen P: Response of human fetal T lymphocytes in xenogeneic mixed leukocyte culture: Phylogeneic and ontogeneic aspects. Immunogenetics 1974;3:272.

    Article  Google Scholar 

  65. Johnston SC, Dustin ML, Hibbs ML, Springer TA: On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules. I Immunol 1990;145:1181.

    CAS  Google Scholar 

  66. Dougherty GJ, Murdoch S, Hogg N: The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immune response. Eur J Immunol 1988;18:35.

    Article  PubMed  CAS  Google Scholar 

  67. Anderson L, Paabo S, Rask L: Is allograft rejection a clue to the mechanism promoting MHC polymorphism? Immunol Today 1987;8:206.

    Article  Google Scholar 

  68. Mandel TE: Transplantation 1988 Immunol Today 1989;10:1

    Article  PubMed  CAS  Google Scholar 

  69. Platt JL, Vercellotti GM, Dalmasso AP, et al: Transplantation of discordant xenografts: A review of progress. Immunol Today 1990;11:450.

    Article  PubMed  CAS  Google Scholar 

  70. Anderson P, Caligluri M, Ritz J, Schlossman SF: CD3 negative natural killer cells express TCR as part of a novel molecular complex. Nature 1989;341:159.

    Article  PubMed  CAS  Google Scholar 

  71. Wiesman AM, Baniyash M, Hou D, Samelson LE, Burgess WH, Klausner RD: Molecular cloning of the zeta chain of the T cell antigen receptor. Science 1988;239:1018.

    Article  Google Scholar 

  72. Janeway CA: Comment. Nature 1989;341:108.

    Article  PubMed  CAS  Google Scholar 

  73. Trinchieri G. Biology of natural killer cells. Adv Immunol 1989;47:187.

    Article  PubMed  CAS  Google Scholar 

  74. Perussia B: Lymphokine-activated killer cells, natural killer cells and cytokines. Curr Opin Immunol 1991;3:49.

    Article  PubMed  CAS  Google Scholar 

  75. Lanier LL, Phillips JH: Natural killer cells. Curr Opin Immunol 1992;4:38.

    Article  PubMed  CAS  Google Scholar 

  76. Lanier LL, Chang C, Azuma M, Ruitenberg JJ, Hemperly JJ, Phillips JH: Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). J Immunol 1991;146:4421.

    PubMed  CAS  Google Scholar 

  77. Lewis CE, McGee JO: Natural killer cells in tumor biology. in Lewis CE McGee JO (eds). The Natural Killer Cell. Oxford, IRL Press, 1992, p 176.

    Google Scholar 

  78. Welsh RM, Vargas-Cortes M: Natural killer cells in viral infection; in Lewis CE, McGee JO (eds). The Natural Killer Cell. Oxford, IRL Press 1992, p 108.

    Google Scholar 

  79. Thiele DL, Lipsky PE: The role of cell surface recognition structures in the initiation of MHC-unrestricted ‘promiscuous’ killing by T cells. Immunol Today 1989;10:375.

    Article  PubMed  CAS  Google Scholar 

  80. Tolone G, del Guercio P, Binaghi R, Biozzi G: Kinetics of phagocytosis of bacteria opsonized with natural or immune antibodies. Int Arch Allergy 1970;37:344.

    CAS  PubMed  Google Scholar 

  81. Stiffel C, del Guercio P, Mouton D: Relations entre la phagecytose des hématies de mouton ou de rat et le taux des anticorps naturels ou immuns chez la souris. Pathol Biol 1968;16:415.

    PubMed  CAS  Google Scholar 

  82. Biozzi G, Stiffel C, Halpern B, Mouton D: Lack of action of serum opsonins in phagocytosis of inert particles by cells of reticule-endothelium system. Proc Soc Exp Biol Med 1963;112:1017.

    PubMed  CAS  Google Scholar 

  83. Ljungren HG, Karre K: In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today 1990;11:237.

    Article  Google Scholar 

  84. Storkus WJ, Salter RD, Alexander J, et al.: Class I-induced resistance to natural killing: Identification of nonpermissive residues in HLA-A2. Proc Natl Acad Sci USA 1991;88:5989.

    Article  PubMed  CAS  Google Scholar 

  85. Storkus WJ, Alexander J, Payne JA, Dawson JR, Cresswell P: Reversal of natural killer susceptibility in target cells expressing transfected class I HLA genes. Proc Natl Acad Sci USA 1989;86:2361.

    Article  PubMed  CAS  Google Scholar 

  86. Chen CH, Sowder JT, Lahti JM, Cihak J, Losch H, Cooper MD: TCR3: A third T-cell receptor in the chicken. Proc Natl Acad Sci USA 1989: 86:2351.

    Article  PubMed  CAS  Google Scholar 

  87. Janis EM, Kaufmann SHE, Schartz RH, Pardoll DM: Activation of y8 T cells in the primary immune response toMycobacterium tuberculosis. Science 1989;244:713.

    Article  PubMed  CAS  Google Scholar 

  88. Holoshitz J, Koning F, Coligan JE, De Bruyn J, Strober S: Isolation of CD4-CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature 1989;339:226.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Medicine, University of California at San Diego, 9500 Gilman Drive, 92093-0961, La Jolla, Calif., USA

    Paolo del Guercio

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del Guercio, P. The self and the nonself: Immunorecognition and immunologic functions. Immunol Res 12, 168–182 (1993). https://doi.org/10.1007/BF02918302

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