The Structural Basis of CD4 — MHC Class II Interactions: Coreceptor Contributions to T Cell Receptor Antigen Recognition and Oligomerization-Dependent Signal Transduction
During thymic differentiation, precursor T lymphocytes committed to the αβ receptor lineage differentiate along two distinct pathways into mature cells distinguished by the mutually exclusive expression of either the CD4 or CD8 cell surface glycoproteins (Reinherz et al. 1980; Reinherz and Schlossman 1980; Fitch 1986; von Boehmer 1988). Early studies of these two lymphocyte subpopulations (CD4+ and CD8+) suggested an association between the functional behavior of a T cell and its expression of either CD4 or CD8, with the former associated with B cell helper activity or delayed type hypersensitivity and the latter with cytotoxic activity. As the importance of class I and class II major histocompatibility complex (MHC) proteins in antigen recognition by αβ T cells became apparent, several investigators examined whether the best correlation of CD4 and CD8 expression was with effector function or, alternatively, with specificity of MHC molecule recognition. Expression of CD8 was found to be tightly linked with reactivity to class I MHC molecules, whereas expression of CD4 was associated with reactivity to class II MHC antigens, irrespective of the helper/cytotoxic behavior of the T cells being studied (Okada and Henney 1980; Swain 1981; Engleman et al. 1981; Biddison et al. 1982; Krensky et al. 1982; Meuer et al. 1982; Spits et al. 1982; Swain 1983; Swain et al. 1983; Fitch 1986; Bierer et al. 1989).
KeywordsMajor Histocompatibility Complex Major Histocompatibility Complex Class Major Histocompatibility Complex Antigen Coreceptor Function Major Histocompatibility Complex Class Specificity
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- Bowman MR, MacFerrin KD, Schreiber SL, Burakoff SJ (1990) Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. Proc Natl Acad Sci USA, 87: 9052–9056PubMedCrossRefGoogle Scholar
- Dialynas DP, Wilde DB, Marrack P, Pierres A, Wall KA, Havran W, Otten G, Loken MR, Pierres M, Kappler J, Fitch FW (1983) Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev 74: 29–56PubMedCrossRefGoogle Scholar
- Fleury S, Thibodean J, Croteau G, Labrecque N, Aronson H-E, Cantin F, Long EO, Sékaly R-P (1995) Polymorphism in the β2 domain of HLA-DR affects the interaction with CD4. J Exp Med 182 (in press)Google Scholar
- König R, Shen X, Germain RN (1995) Involvement of both MHC Class II a and β chains in CD4 function indicates a role for ordered oligomeritation in T Cell activation. J Exp Med 182 (in press)Google Scholar
- Moebius U, Clayton LK, Abraham S, Diener A, Yunis JJ, Harrison SC, Reinherz EL (1992a) Human immunodeficiency virus gp120 binding C’C” ridge of CD4 domain 1 is also involved in interaction with class II major histocompatibility complex molecules. Proc Natl Acad Sci USA 89:12008–12012PubMedCrossRefGoogle Scholar
- Moebius U, Clayton LK, Abraham S, Harrison SC, Reinherz EL (1992b) The human immunodeficiency virus gp120 binding site on CD4: delineation by quantitative equilibrium and kinetic binding studies of mutants in conjunction with a high-resolution CD4 atomic structure. J Exp Med 176: 507–517PubMedCrossRefGoogle Scholar
- Spits H, Borst J, Terhorst C, de Vries JE (1982) The role of T cell differentiation markers in antigen-specific and lectin-dependent cellular cytotoxicity mediated by T8+ and T4+ human cytotoxic T cell clones directed at class I and class II MHC antigens. J. Immunol., 129: 1563–1569PubMedGoogle Scholar
- Wilde DB, Marrack P, Kappler J, Dialynas DP, Fitch FW (1983) Evidence implicating L3T4 in class II MHC antigen-reactivity: monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol 131: 2178–2183PubMedGoogle Scholar