Original Article

Journal of Investigative Dermatology (1990) 94, 118s–121s; doi:10.1111/1523-1747.ep12876078

The Class II Major Histocompatibility Complex Antigen Deficiency Syndrome: Consequences of Absent Class II Major Histocompatibility Antigens for Lymphocyte Differentiation and Function

Loran T Clement

Department of Pediatrics, UCLA School of Medicine, Los Angeles, California, U.S.A.

Top

Abstract

The class II major histocompatibility complex antigen deficiency syndrome is a rare immunodeficiency disease associated with defective expression of the class II antigens encoded for by the major histocompatibility complex. Clinically, this syndrome is manifest as a combined immuno-deficiency presenting early in life, and affected individuals are susceptible to a variety of severe and/or opportunistic infections. Chronic, severe diarrhea and malabsorption are also characteristically found, and death is common within the first few years of life. Although the precise molecular lesions responsible for the failure of membrane antigen expression in this syndrome have not yet been identified, the pathogenetic mechanisms involve regulatory defects in the transcription of structural genes encoding for class II antigens. The absence of class II MHC antigens results in profound abnormalities in lymphocyte function and differentiation. Of central importance is the defective MHC-restricted interactions between CD4+ "helper" T lymphocytes and the various types of antigen-presenting cells found in the skin and elsewhere. The absence of class II MHC antigens also appears to alter the ability of affected B cells to be activated by a variety of membrane-mediated stimuli, and it profoundly disrupts both the intrathymic development and post-thymic differentiation of immunoregulatory T cells. This "experiment of nature" thus demonstrates the critical role of class II MHC antigens in the proper development and function of the immune system.

Top

References

  1. Touraine, J-L, Betuel, H, Gouillet, G, Jeune, M: Combined immunodeficiency disease associated with absence of cell-surface HLA-A and -B antigens. J Pediatr 1978 93: 47–51,  | PubMed | ISI | ChemPort |
  2. Schuurman, RKB, van Rood, JJ, Vossen, JM, Schellekens, PTA, Feltkamp-Vroom, TM, Doyer, E, Gmelig-Meyling, F, Visser, HKA: Failure of lymphocyte-membrane HLA-A and -B expression in two siblings with combined immunodeficiency. Clin Immunol Immunopath 1979 14: 418–434,
  3. Griscelli, C, Durandy, A, Virelizier, JL: Impaired cell to cell interaction in partial combined immunodeficiency with variable expression of HLA antigens. In: Seligmann M, Hitzig WH (eds.). Primary Immunodeficiencies 1980, Elsevier/North Holland, Amsterdam, pp 499–503,
  4. Hadam, MR, Dopfer, R, Dammer, G, Peter, H-H, Schlesier, M, Muller, C, Niethammer, D: Defective expression of HLA-DR region determinants in children with congenital agammaglobulinemia and malabsorption. In: Albert ED (ed.), Histocompatibility Testing 1984 1984, Springer-Verlag, Heidelberg, pp 645–650,
  5. Touraine, J-L, Marseglia, G-L, Betuel, H: Thirty international cases of bare lymphocyte syndrome: Biological significance of HLA antigens. Exp Hematol 1985 13: 86–87,
  6. McDevitt, HO: Functional analysis of Ia antigens in relation to genetic control of the immune response. In: Katz DH, Benacerraf B (eds.), The Role of the Products of the Histocompatibility Gene Complex in Immune Responses 1976, pp Academic Press, New York, 257–265,
  7. Benacerraf, B: Role of MHC gene products in immune regulation. Science 1981 212: 1229–1235,  | PubMed | ISI | ChemPort |
  8. Schwartz, RH: The role of gene products of the major histocompatibility complex in T cell activation and cellular interactions. In: Paul WE (ed.), Fundamental Immunology 1984, Raven Press, New York, pp 379–403,
  9. Longo, DL, Schwartz, RH: T-cell specificity for H-2 and Ir-region phenotype correlates with the phenotype of thymic antigen-presenting cells. Nature 1980 287: 44–46,  | Article | PubMed | ISI | ChemPort |
  10. Kruisbeek, AM, Mond, JJ, Fowlkes, BJ, Carmen, JA, Bridges, S, Longo, DL: Absence of the Lyt-2-, L3T4+ lineage of T cells in mice treated neonatally with anti-1-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function. J Exp Med 1985 161: 1029–1047,  | Article | PubMed | ISI | ChemPort |
  11. Niederhuber, JE, Frelinger, JA, Dugan, E, Coutinho, A, Shreffler, DC: Effects of anti-la serum on mitogenic responses. Inhibition of the proliferative response to B cell mitogen, LPS, by specific anti-la sera. J Immunol 1975 115: 1672–1677,
  12. Forsgren, S, Pobor, G, Coutinho, A, Pierres, M: The role of I-A/E molecules in B lymphocyte activation. I. Inhibition of lipopolysaccharide-induced responses by monoclonal antibodies. J Immunol 1984 133: 1204–1210,
  13. Clement, LT, Tedder, TF, Gartland, GL: Antibodies reactive with class II antigens encoded for by the major histocompatibility complex inhibit human B cell activation. J Immunol 1986 136: 2375–2381,
  14. Bonagura, VR, Agostino, N, Crow, MK, Pernis, B: Anti-immunoglobulin stimulation of human B lymphocytes is inhibited by anti-class II major histocompatibility complex antibodies. Cell Immunol 1985 96: 442–447,
  15. Durandy, A, Oury, C, Griscelli, C, Dumez, Y, Oury, JF, Henrion, R: Prenatal testing for inherited immune deficiencies by fetal blood sampling. Prenatal Diagnosis 1982 2: 109–113,
  16. Durandy, A, Dumez, Y, Griscelli, C: Antenatal diagnosis of severe hereditary immunologic deficiency syndromes. Arch Fr Pediatr 1985 42: 163–167,
  17. Salter, RD, Alexander, J, Levine, F, Pious, D, Cresswell, P: Evidence for two trans-acting genes regulating HLA class II antigen expression. J Immunol 1985 135: 4235–4238,
  18. de Preval, C, Lisowska-Grospierre, B, Loche, M, Griscelli, C, Mach, B: A trans-acting class II regulatory gene unlinked to the MHC controls expression of HLA class II genes. Nature 1985 318: 291–293,  | Article | PubMed | ChemPort |
  19. Lisowska-Grospierre, B, Charron, DJ, de Preval, C, Durandy, A, Griscelli, C, Mach, B: A defect in the regulation of major histocompatibility complex class II gene expression in human HLA-DR negative lymphocytes from patients with combined immunodeficiency syndrome. J Clin Invest 1985 76: 381–385,
  20. de Preval, C, Hadam, MR, Mach, B: Regulation of genes for HLA class II antigens in cell lines from patients with severe combined immunodeficiency. New Engl J Med 1988 318: 1295–1300,
  21. Clement, LT, Plaeger-Marshall, S, Haas, A, Saxon, A, Martin, AM: Bare lymphocyte syndrome: Consequences of absent class II major histocompatibility antigen expression for B lymphocyte differentiation and function. J Clin Invest 1988 81: 669–675,
  22. Plaeger-Marshall, S, Haas, A, Clement, LT, Giorgi, JV, Chen, ISY, Quan, S, Gatti, RA, Stiehm, ER: Interferon-induced expression of class II major histocompatibility antigens in the major histocompatibility complex (MHC) class II deficiency syndrome. J Clin Immunol 1988 8: 285–295,
  23. Rijkers, GT, Roord, JJ, Koning, F, Kuis, W, Zegers, BJM: Phenotypical and functional analysis of B lymphocytes of two siblings with combined immunodeficiency and defective expression of major histocompatibility complex (MHC) class II antigens on mononuclear cells. J Clin Immunol 1987 7: 98–106,
  24. Maffei, A, Scarpellino, L, Bernard, M, Carra, G, Jotterand-Bellamo, M, Guardiola, J, Accolla, RS: Distinct mechanisms regulate MHC class II gene expression in B cell and macrophages. J Immunol 1987 139: 942–948,
  25. Woodward, JG, Omer, KW, Stuart, M: MHC class II transcription in different mouse cell types. Differential requirement for protein synthesis between B cell and macrophages. J Immunol 1989 142: 4062–4069,
  26. Clement, LT, Giorgi, JV, Plaeger-Marshall, S, Haas, A, Stiehm, ER, Martin, AM: Abnormal differentiation of immunoregulatory T lymphocyte subpopulations in the major histocompatibility complex (MHC) class II antigen deficiency syndrome. J Clin Immunol 1988 8: 503–512,
  27. Hadam, MR, Dopfer, R, Peter, H-H, Niethammer, D: Congenital agammaglobulinemia associated with lack of expression of HLA-D region antigens. In: Griscelli C, Vossen JM (eds.), Progress in Immunodeficiency Research and Therapy I 1984, Amsterdam, Excerpta Medica Elsevier, pp 43–50,
  28. Griscelli, C, Durandy, A, Virelizier, JL, Grospierre, B, Oury, C, de Saint-Basile, G, Couillin, P, Niaudet, P, Betuel, H, Hors, J, Lepage, V, Colombani, J: Impaired cell to cell interaction in partial combined immunodeficiency with defective synthesis and membrane expression of HLA antigens. In: Touraine J-L, Gluckman E, Griscelli C (eds.), Bone Marrow Transplantation in Europe II 1981, Amsterdam, Excerpta Medica Elsevier, pp 194–200,
  29. Schuurman, HJ, van de Wijngaert, FP, Huber, J, Schuurman, RKB, Zegers, BJM, Roord, JJ, Kater, L: The thymus in "bare lymphocyte" syndrome: Significance of expression of major histocompatibility complex antigens on thymic epithelial cells in intrathymic T-cell maturation. Human Immunol 1985 13: 69–82,
  30. Blue, ML, Daley, JF, Levine, H, Schlossman, SF: Class II major histocompatibility complex molecules regulate the development of T4 + T8—inducer phenotype of cultured human thymocytes. Proc Natl Acad Sci USA 1985 82: 8178–8183,
  31. Larocca, LM, Piantelli, M, Maggiano, N, Musiani, P: T-cell surface marker expression by immature human thymocytes in culture: Role of IA+ accessory cells. J Immunol 1987 138: 2410–2416,
  32. Tedder, TF, Cooper, MD, Clement, LT: Human lymphocyte differentiation antigens HB-10 and HB-11. II. Differential production of B cell growth and differentiation factors by distinct helper T cell subpopulations. J Immunol 1985 134: 2989–2995,
  33. Clement, LT, Yamashita, N, Martin, AM: The functionally distinct subpopulations of human CD4 + helper/inducer T lymphocytes defined by anti-CD45R antibodies derive sequentially from a differentiation pathway that is regulated by activation-dependent postthymic differentiation. J Immunol 1988 141: 1464–1470,  | PubMed | ISI | ChemPort |
  34. Clement, LT, Grossi, CE, Gartland, GL: Morphologic and phenotypic features of the subpopulation of Leu-2 + cells that suppresses B cell differentiation. J Immunol 1984 133: 2461–2468,  | PubMed | ChemPort |
  35. Wilde, DB, Marrack, P, Kappler, J, Dialynas, DP, Fitch, FW: Evidence implicating L3T4 in class II MHC antigen-reactivity: Monoclonal antibody GK1.5 (anti-L3T4) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol 1983 131: 2178–2183,  | PubMed | ISI | ChemPort |
  36. Ceredig, R, Dialynas, DP, Fitch, FW, MacDonald, HR: Precursors of T cell growth factor producing cells in the thymus: Ontogeny, frequency, and quantitative recovery in a subpopulation of phenotypically mature thymocytes defined by monoclonal antibody GK-1.5. J Exp Med 1983 158: 1654–1666,  | Article | PubMed | ISI | ChemPort |
  37. Kashahara, T, Hooks, JJ, Dougherty, SF, Oppenheim, JJ: Interleukin 2-mediated immune interferon production by human T cells and T cell subsets. J Immunol 1983 130: 1784–1789,
  38. Durandy, A, Mangeney, M, Griscelli, C, Forveille, M, Le Deist, F, Fischer, A: Activation of genetically major histocompatibility complex (MHC) class II-deficient B lymphocytes. J Clin Immunol 1989 9: 125–131,

Extra navigation

.
ADVERTISEMENT