Clonotypic surface structure on human T lymphocytes: functional and biochemical analysis of the antigen receptor complex.
Recent studies using cloned antigen-specific T lymphocytes and monoclonal antibodies directed at their various surface glycoprotein components have led to identification of the human T cell antigen receptor as a surface complex comprised of a clonotypic 90KD Ti heterodimer and the monomorphic 20/25KD T3 molecules. Approximately 30,000-40,000 Ti and T3 molecules exist on the surface of human T lymphocytes. These glycoproteins are acquired and fully expressed during late thymic ontogeny, thus providing the structural basis for immunologic competence. The alpha and beta subunits of Ti bear no precursor-product relationship to one another and are encoded by separate genes. The presence of unique peptides following proteolysis of different Ti molecules isolated by noncrossreactive anticlonotypic monoclonal antibodies supports the notion that variable regions exist within both the alpha and beta subunits. Moreover, N-terminal amino acid sequencing of the Ti beta subunit shows that it bears homology to the first V-region framework of immunoglobulin light chains and represents the product of a gene that rearranges specifically in T lymphocytes. Soluble or Sepharose-bound anti-Ti monoclonal antibodies, like physiologic ligand (antigen/MHC), enhanced proliferative responses to purified IL-2 by inducing a 6-fold increase in surface IL-2 receptor expression. In contrast, only Sepharose-bound anti-Ti or physiologic ligand triggered endogenous clonal IL-2 production and resulted in subsequent proliferation. The latter was blocked by antibodies directed at either the IL-2 receptor or IL-2 itself. These results suggest that induction of IL-2 receptor expression but not IL-2 release occurs in the absence of T3-Ti receptor crosslinking. Perhaps more importantly, the findings demonstrate that antigen-induced proliferation is mediated through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors.
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface / Q000032:analysis; D002462:Cell Membrane / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005796:Genes; D006801:Humans; D008285:Major Histocompatibility Complex; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell