Abstract
T lymphocytes that express CD4 respond to foreign antigens presented in the context of syngeneic class II MHC molecules. T cells responding to allogeneic class II MHC molecules generally express CD4, but exceptions are observed. We show that the same receptor on a cloned T cell line recognizes both foreign antigen associated with self-class II MHC and nonself-class II MHC molecules. The role of CD4 in these recognition responses appears to be to bind to class II MHC molecules and, through association with the T cell receptor recognizing the same class II MHC molecule, to effectively activate the T cell. It is proposed on the basis of these two findings that the high ligand multiplicity of alloantigens recognized in unmodified form by high affinity anti-nonself-MHC receptors can explain the finding of CD8+ T cells responding to nonself-class II MHC molecules, as well as the inability of anti—CD4 to inhibit such nonself-class II MHC recognition completely. Finally, data will be presented to suggest that class II may also play a role in selecting the functional activity elicited in response to a protein antigen in vivo. These data show that the CD4:T cell receptor complex interaction with the complex of foreign antigen and self-MHC is the critical event in initiating most immune responses and may also play a role in controlling their functional outcome.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aparicio, P., Jaraquemada, D., and Lopez de Castro, J.A.: Alloreactive cytolytic T cell clones with dual recognition of HLA-B27 and HLA-DR2 antigens. Selective involvement of CD8 in their class I directed cytotoxicity. J. Exp. Med. 165:428, 1987.
Asano, Y., and Hodes, R.J.: T cell regulation of B cell activation. Cloned Lyt-1+2- suppressor cells inhibit the major histocompatibility complex restricted interactions of T helper cells with B cells and/or accessory cells. J. Exp. Med. 158:1178, 1983.
Bottomly, K., Kaye, J., Jones, F., III, Jones, B., and Janeway, C.A., Jr.: A cloned antigen-specific Ia-restricted Lyt-1+, 2- T cell with suppressive activity. J. Mol. Cell. Immunol. 1:42, 1983.
Bottomly, K., and Janeway, C.A.: Selected populations of alloreactive T cells contain helper T cells but lack ThId, an antigen-specific helper T cell required for dominant production of the T15 idiotype. Eur. J. Immunol. 11:270, 1981.
Cher, D.J., and Mosmann, T.R.: Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by Th 1 clones. J. Immunol. 138: 3688, 1987.
Fazekas de St. Groth, B., Gallagher, P.F., and Miller, J.F.A.P.: Involvement of Lyt-2 and L3T4 in activation of hatpen-specific Lyt-2+, L3T4+ T cell clones. Proc. Nat. Acad. Sci. (USA) 83:2584, 1986.
Gay, D., Kappler, J., and Marrack, P.: L3T4 interacts with class II molecules on target cells. Ann. Inst. Pasteur (Immunology) 138.127, 1987.
Golding, H., and Singer, A.: Specificity, phenotype and precursor frequency of primary cytolytic T lymphocytes specific for class II major histocompatibility antigens. J, Immunol. 135:1610, 1985.
Greenstein, J.L., Malissen, B., and Burakoff, S.F.: Role of L3T4 in antigen-driven activation of a class I-specific T cell hybridoma. J. Exp. Med. 162:369, 1985.
Hague, S., Saizawa, K., Rojo, J., and Janeway, C.A., Jr.: The influence of valence on the functional activities of monoclonal anti-L3T4 antibodies: discrimination of signaling from other effects. Submitted for publication.
Heber-Katz, E., and Wilson, D.B.: Sheep red blood cell-specific helper activity in rat thoracic duct lymphocyte populations positively selected for reactivity to strong specific histocompatibiltiy alloantigens. J. Exp. Med. 143:701, 1976.
Janeway, C.A., Jr., and Katz, M.E.: The immunobiology of the T cell response to Mls-locus disparate stimulator cells. I. Unidirectionality, new strain combinations, and the role of Ia antigens. J. Immunol. 134:2057, 1985.
Janeway, C.A., Jr., Lerner, E.A., Conrad, P.J., and Jones, B.: The precision of self and nonself major histocompatibility complex encoded antigen recognition by cloned T cells. Behring Inst. Mitteilungen 70:200, 1982.
Janeway, C.A., Jr., Hague, S., Smith, L.A., and Saizawa, K.: The role of the murine L3T4 molecule in T cell activation: Differential effects of anti-L3T4 on activation by monoclonal anti-receptor antibodies: J. Mol. Cell. Immunol. 3:121, 1987.
Jones, B., Khavari, P.A., Conrad, P.J., and Janeway, C.A., Jr.: Differential effects of antibodies to Lyt-2 and L3T4 on cytolysis by cloned, Ia-restricted T cells expressing both proteins. J. Immunol. In press.
Kaye, J., and Janeway, C.A., Jr.: The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-lined heterodimer from a helper T cell clone blocks activation by either allogeneic-Ia or antigen and self-Ia. J. Exp. Med. 159:1397, 1984.
Kim, J., Woods, A., Becker-Dunn, E., and Bottomly, K. Distinct functional phenotypes of cloned Ia-restricted helper T cells. J. Exp. Med. 162: 188, 1985.
Kupfer, A., Singer, S.J.,Janeway, C.A., Jr., and Swain, S.L.: Co-clustering of CD4 (L3T4) with the T cell receptor is induced by specific direct interaction of helper T cells and antigen presenting cells. Proc. Nat. Acad. Sci. (USA). In press.
Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A., and Coffman, R.L.: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136:2340, 1986.
Ratzlaff, R., Porcelli, S., Bottomly, K., Askenase, P.W., and Janeway, C.A., Jr. Unpublished observations.
Rojo, J., and Janeway, C.A., Jr.: The biological activity of anti-T cell receptor variable region antibodies is determined by the epitope recognized. Submitted for publication.
Saizawa, K., Rojo, J., Janeway, C.A., Jr.: Physical association of CD4 and the CD3:a:ß T cell receptor. Nature (Lond). In press.
Schilham, M.W., Lang, R., Benner, R., Zinkernagel, R.M., and Hengartner, H.: Characterization of an Lyt-2+ alloreactive cytotoxic T cell clone specific for H-2Db that cross-reacts with I-Ek. J. Immunol. 137:2748, 1986.
Sredni, B, and Schwartz, H.: Antigen-specific, proliferating T lymphocyte clones. Methodology, specificity, MHC restriction and alloreactivity. Immunol. Rev. 54:187, 1981.
Swain, S.A.: T cell subsets and the recognition of MHC class. Immunol. Rev. 74:129, 1983.
Tite, J.P., and Janeway, C.J., Jr.: Cloned helper T cells can kill B lymphoma cells in the presence of specific antigen: Ia restriction and cognate vs. non-cognate interactions in cytolysis. Eur. J. Immunol. 14:878, 1984.
Tite, J.P., Powell, M.B., and Ruddle, N.H.: Protein-antigen specific Ia-restricted cytolytic T cells: Analysis of frequency, target cell susceptibility and mechanism of cytolysis. J. Immunol 135:25, 1985.
Tite, J.P., Sloan, A, and Janeway, C.A., Jr.: The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal. J. Mol. Cell, Immunol. 2:179, 1986.
Tite, J.P., H.G. Foellmer, J.A. Madri, and C.A. Janeway, Jr. 1987. Inverse Ir gene control of the antibody and T cell proliferative responses to human basement membrane collagen. Submitted for publication.
Wilson, D.B.: Immunologic reactivity to major histocompatibility alloantigens: HARC, effector cells and the problem of memory. Prox. Immunol. 2:45, 1974.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Springer Science+Business Media New York
About this chapter
Cite this chapter
Janeway, C.A., Portoles, P., Tite, J.P., Rojo, J., Saizawa, K., Jones, B. (1987). Recognition of MHC Class II Antigens by the CD4: T Cell Receptor Complex. In: David, C.S. (eds) H-2 Antigens. NATO ASI Series, vol 144. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-0764-9_44
Download citation
DOI: https://doi.org/10.1007/978-1-4757-0764-9_44
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-0766-3
Online ISBN: 978-1-4757-0764-9
eBook Packages: Springer Book Archive