The main objective of this proposal is to study molecular interactions between Class I heacy chain and two cell surface components possibly involved in MHCrestricted antigen recognition by T cells: i) a 38 kDa molecule found on Sezary leukemia and alloactivated T cells; and ii) T8 molecule present on a subpopulation of thymocytes and mature T cells. Our preliminary results suggest that beta 2M-free HLA heavy chain is noncovalently associated with a 38 kDa molecule found on the surface of Sezary leukemia and normal alloactivated T cells. The 38 kDa component of this 38-43 kDa heterodimer displays structural homology to the beta-chain of a """"""""classical"""""""" alpha-beta T cell receptor expressed on the same leukemia cells. Like alpha- beta receptor, the 38-43 kDa heterodimer is associated with T3 molecular complex. The 38 kDa molecules expressed on T leukemia cells from three different sources vary in their molecular mass and pI thus suggesting a clonal nature of the 38 kDa molecule. We assume therefore that this 38kDa molecule may be involved in the process of antigen recognition by T cells. Likewise, the T8 molecule is thought to be involved in MHC- restricted T cell recognition. In accordance with this, our results indicate that on the surface of normal peripheral blood T cells the T8 molecule is noncovalently associated with beta 2M-free HLA heavy chain. To determine whether these molecular complexes formed on the T cell surface by HLA heavy chains have functional consequences, we propose to investigate them by serological, genetical and biochemical means. More specifically, we suggest the following course of studies: 1. Generation of monoclonal and heteroantibodies against 38 kDa molecule expressed on leukemia and normal alloactivated T cells. 2. Cloning the gene coding for the 38 kDa molecule. 3. Further elucidation of the association between HLA and 38 kDa molecules. 4. Identification of correlation between cellular immune functional characteristics and expression of 38 kDa molecule. 5. Biochemical characterization of the T8-HLA molecular complex. 6. Determination of the presence of T8-HLA molecular complexes in different functional subsets of T8-positive cells.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Immunobiology Study Section (IMB)
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Public Health Research Institute
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Demaria, S; Schwab, R; Bushkin, Y (1992) The origin and fate of beta 2m-free MHC class I molecules induced on activated T cells. Cell Immunol 142:103-13
Bushkin, Y; Demaria, S; Mohagheghpour, N et al. (1990) Activation of human CD8-positive T cells via the CD8/HLA class I complex. Cell Immunol 126:185-95
Bushkin, Y; Demaria, S; Le, J M et al. (1988) Physical association between the CD8 and HLA class I molecules on the surface of activated human T lymphocytes. Proc Natl Acad Sci U S A 85:3985-9