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Imunology and the Challenge of Transplantation

  • Rebeca Alonso Arias
  • Antonio López-Vázquez
  • Carlos López-LarreaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 741)

Abstract

Transplantation of tissues or organs between individuals who are not genetically related often leads to rejection by the recipient. The human genes responsible for this process are located on the short arm of the chromosome 6 and are called Major Histocompatibility Complex (MHC). Six main loci have been identified in the human MHC: HLA-A, HLA-B and HLA-C belong to the HLA class I, while HLA-DP, HLA-DQ and HLA-DR belong to HLA class II. The physiological function of MHC molecules is to present peptides to the T cells. Indeed, they are integral components of the ligands that recognise most T cells, since the receptor of the T cell (TCR) has specificity for complexes of foreign antigenic peptides, and self-MHC molecules. Thus the proteins of the MHC are responsible for the body being able to distinguish between its own and foreign cells, known as self-tolerance and consequently are the proteins which determine the evolution of transplants. The special case of foreign MHC antigen recognition is known as allorecognition and consists of the capacity of T cells to recognise peptide/MHC complexes with which they have not been in contact during the process of maturation in the thymus. There are two mechanisms of allorecognition, direct and indirect; both can lead to rejection of the transplant. Direct recognition prevails during the first few weeks or months after transplantation, and is caused by the APCs of the donor. These cells start disappearing from the transplanted organ and indirect recognition becomes important. There is evidence that the indirect pathway is sufficient to mediate both acute and chronic rejection. In this chapter we will describe fundamental aspects of the MHC system, as well as, specifically, its involvement in the allogenic response of the immune system against organ transplants.

Keywords

Major Histocompatibility Complex Major Histocompatibility Complex Class Major Histocompatibility Complex Molecule Major Histocompatibility Complex Region Major Histocompatibility Complex Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Gibson T, Medawar PB. The fate of skin homografts in man. J Anat 1943; 77: 299–310.PubMedGoogle Scholar
  2. 2.
    Snell GD, Higgins GF. Alleles at the histocompatibility-2 locus in the mouse as determined by tumor transplantation. Genetics. 1951; 36(3): 306–310.PubMedGoogle Scholar
  3. 3.
    Dausset J, Nenna A, Brecy H. Presence of a leukoagglutinin in serum of three leukopenic patients. Sang 1953; 24(5): 410–417.PubMedGoogle Scholar
  4. 4.
    Payne R. The association of febrile transfusion reactions with leuko-agglutinins. Vox Sang 1957; 2(4): 233–241.PubMedCrossRefGoogle Scholar
  5. 5.
    Van Rood J, van Leeuwen, Eernisse JG. Antigens against leukocytes in the serum of pregnant women. Ned Tijdschr Geneeskd 1959; 103: 1928–1931.PubMedGoogle Scholar
  6. 6.
    Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 1969; 280(14): 735–739.PubMedCrossRefGoogle Scholar
  7. 7.
    Zinkernagel RM, Doherty PC. Restriction of in vitro T-cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 1974; 248: 701–702.PubMedCrossRefGoogle Scholar
  8. 8.
    Campbell RD, Trowsdale J. Map of the human MHC. Immunol Today 1993; 14(7): 349–352.PubMedCrossRefGoogle Scholar
  9. 9.
    Klein J, Sato A. The HLA system. N Engl J Med 2000; 343(11): 782–786.PubMedCrossRefGoogle Scholar
  10. 10.
    Marsh SG, Albert ED, Bodmer WF et al. Nomenclature for factors of the HLA system, 2010. Tissue Antigens 2010; 75: 291–455.PubMedCrossRefGoogle Scholar
  11. 11.
    Strominger JL, Humphreys RE, McCune JM et al. The immunoglobulin-like structure of human histocompatibility antigens. Fed Proc 1976; 35: 1177–1182.PubMedGoogle Scholar
  12. 12.
    York IA, Rock KL. Antigen processing and presentation by the class I major histocompatibility complex. Annu Rev Immunol 1996; 14: 369–396.PubMedCrossRefGoogle Scholar
  13. 13.
    Brown JH, Jardetzky TS, Gorga JC et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993; 364: 33–39.PubMedCrossRefGoogle Scholar
  14. 14.
    Bahram S, Bresnahan M, Geraghty DE et al. A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci USA 1994; 91: 6259–6263.PubMedCrossRefGoogle Scholar
  15. 15.
    Simpson E, Scott D, James E et al. Minor Hantigens: genes and peptides. Transpl Immunol 2002; 10: 115–123.PubMedCrossRefGoogle Scholar
  16. 16.
    Ruggeri L, Capanni M, Urbani E et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097–2100.PubMedCrossRefGoogle Scholar
  17. 17.
    Pamer E, Cresswell P. Mechanisms of MHC class I restricted antigen processing. Ann Rev Immunol 1998; 16: 323–358.CrossRefGoogle Scholar
  18. 18.
    Rock KL, Goldberg AL. Degradation of cell proteins and generation of MHC class I-presented peptides. Ann Rev Immunol 1999; 17: 739–779.CrossRefGoogle Scholar
  19. 19.
    Geuze HJ. The role of endosomes and lysosomes in MHC class II functioning. Immunol Today 1998; 19: 282–287.PubMedCrossRefGoogle Scholar
  20. 20.
    Villadangos JA, Ploegh HL. Proteolysis in MHC class II antigen presentation: who’s in charge? Immunity 2000; 12: 233–239.PubMedCrossRefGoogle Scholar
  21. 21.
    Engelhard VH. Structure of peptides associated with class I and class II MHC molecules. Ann Rev Immunol 1994; 12: 181–207.CrossRefGoogle Scholar
  22. 22.
    Garcia KC, Teyton L, Wilson IA. Structural basis of T-cell recognition. Ann Rev Immunol 1999; 17: 369–397.CrossRefGoogle Scholar
  23. 23.
    Reiser JB, Darnault C, Guimezanes A et al. Crystal structure of a T-cell receptor bound to an allogeneic MHC molecule. Nat Immunol 2000; 1(4): 291–297.PubMedCrossRefGoogle Scholar
  24. 24.
    Luz JG, Huang M, Garcia KC et al. Structural comparison of allogeneic and syngeneic T-cell receptor-peptide-major histocompatibility complex complexes: a buried alloreactive mutation subtly alters peptide presentation substantially increasing V(beta) interactions. J Exp Med 2002; 195(9): 1175–1186.PubMedCrossRefGoogle Scholar
  25. 25.
    Felix NJ, Allen PM. Specificity of T-cell alloreactivity. Nature Reviews Immunol 2007; 7: 942–955.CrossRefGoogle Scholar
  26. 26.
    Archbold JK, Ely LK, Kjer-Nielsen L et al. T-cell allorecognition and MHC restriction—A case of Jekyll and Hyde? Mol Immuno 2008; 45(3): 583–598.CrossRefGoogle Scholar
  27. 27.
    Afzali B, Lechler RI, Hernandez-Fuentes MP. Allorecognition and the alloresponse: clinical implications. Tissue Antigens 2007; 69(6): 545–556.PubMedCrossRefGoogle Scholar
  28. 28.
    Suchin EJ, Langmuir PB, Palmer E et al. Quantifying the frequency of alloreactive T-cells in vivo: new answers to an old question. J Immunol 2001; 166: 973–981.PubMedGoogle Scholar
  29. 29.
    Afzali B, Lombardi G, Lechler RI. Pathways of major histocompatibility complex allorecognition. Curr Opin Organ Transplant 2008; 13: 438–444.PubMedCrossRefGoogle Scholar
  30. 30.
    Boisgérault F, Liu Y, Anosova N et al. Differential roles of direct and indirect allorecognition pathways in the rejection of skin and corneal transplants. Transplantation 2009; 87: 16–23.PubMedCrossRefGoogle Scholar
  31. 31.
    Benichou G, Thomson AW. Direct versus indirect allorecognition pathways: on the right track. Am J Transplant 2009; 9: 655–656.PubMedCrossRefGoogle Scholar
  32. 32.
    Bevan MJ. High determinants density may explain the phenomenon of alloreactivity. Immunol Today 1984; 5: 128–130.CrossRefGoogle Scholar
  33. 33.
    Elliott TJ, Eisen HN. Cytotoxic T-lymphocytes recognize a reconstituted class I histocompatibility antigen (HLA-A2) as an allogeneic target molecule. Proc Natl Acad Sci USA 1990; 87: 5213–5217.PubMedCrossRefGoogle Scholar
  34. 34.
    Smith PA, Brunmark A, Jackson MR et al. Peptide independent recognition by alloreactive cytotoxic T-lymphocytes (CTL). J Exp Med 1997; 185: 1023–1033.PubMedCrossRefGoogle Scholar
  35. 35.
    Matzinger P, Bevan MJ. Hypothesis: why do so many lymphocytes respond to major histocompatibility antigens? Cell Immunol 1977; 29: 1–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Weber DA, Terrell NK, Zhang Y et al. Requirement for peptide in alloreactive CD4+ T-cell recognition of class II MHC molecules. J Immunol 1995; 154: 5153–5164.PubMedGoogle Scholar
  37. 37.
    Gökmen MR, Lombardi G, Lechler RI. The importance of the indirect pathway of allorecognition in clinical transplantation. Curr Opin Immunol 2008; 20: 568–574.PubMedCrossRefGoogle Scholar
  38. 38.
    Weiss MJ, Guenther DA, Mezrich JD et al. The indirect alloresponse impairs the induction but not maintenance of tolerance to MHC class I-disparate allografts. Am J Transplant 2009; 9: 105–113.PubMedCrossRefGoogle Scholar
  39. 39.
    Lechler RI, Batchelor JR. Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med 1982; 155(1): 31–41.PubMedCrossRefGoogle Scholar
  40. 40.
    Gould DS, Auchincloss H Jr. Direct and indirect recognition: the role of MHC antigens in graft rejection. Immunol Today 1999; 20(2): 77–82.PubMedCrossRefGoogle Scholar
  41. 41.
    Bolton EM, Bradley JA, Pettigrew GJ. Indirect allorecognition: not simple but effective. Transplantation 2008; 85: 667–669.PubMedCrossRefGoogle Scholar
  42. 42.
    Le MA, Goldman M, Abramowicz D. Multiple pathways to allograft rejection. Transplantation 2002; 73: 1373–1381.CrossRefGoogle Scholar
  43. 43.
    Terasaki PI. Humoral theory of transplantation. Am J Transplant 2003; 3: 665–673.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Rebeca Alonso Arias
    • 1
  • Antonio López-Vázquez
    • 1
  • Carlos López-Larrea
    • 1
    • 2
    Email author
  1. 1.Department of ImmunologyHospital Universitario Central de AsturiasOviedoSpain
  2. 2.Fundación Renal “Iñigo Álvarez de Toledo,”MadridSpain

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