Our objectives are: (1) production of monoclonal antibodies (MoAB) to the constant regions of the human T-cell antigen receptor; (2) investigation of functional subsets of T cells and T-cell clones in relationship to the T-cell antigen receptor; (3) analysis of observed differences of T-cell antigen receptor molecules of various leukemic T cell and T-cell lines; and (4) the study of shared epitopes of certain T-cell antigen receptors. The T-cell antigen receptor recently has been described at the protein and gene levels. Studies on polyclonal T-cell populations in health and disease and on large numbers of different T-cell clones will benefit from the availability of constant region markers of the human T-cell antigen receptor. Functionally defined T-cell subsets may respond differently to signals mediated through the T-cell antigen receptor and may possess different types of T-cell antigen receptors. In order to produce MoAb to constant region determinants of the T-cell antigen receptor we will immunize with immunoprecipitates of this molecule. Short sequences corresponding to the constant regions of the two chains of the T-cell antigen receptor will be produced for use as immunogens. Striking structural differences between two T-cell antigen receptors from human T-cell leukemias have been described. The relative contribution of glycosylation and/or protein differences will be studied. We will probe for mRNA with specific beta chain probes. Rearrangements of cDNA will also be assessed. The leukemic cells bearing these two different receptors also responded differently to activation mediated through the T-cell antigen receptor with anti-idiotypic MoAb. Studies will investigate the absence of a proliferative response in one of the leukemic cell types and the possibility that different normal T-cell subsets are represented by the two different T-cell leukemias. Studies of the functional significance of shared determinants of human T-cell antigen receptor will utilize T-cell clones with known antigen specificity and known phenotype in regard to shared determinants of the T-cell antigen receptor. (AG)
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