The study of the activation of murine T lymphocytes has been a major focus of our laboratory. This proposal aims to explore the role of surface proteins other than the antigen/MHC T cell receptor in T cell activation and function. Specifically, through the production of MAb's, our laboratory has identified two related T cell surface proteins (TAP and TAPa) that are involved in the process of cellular activation. Preliminary data suggests that these molecules are distinct from known T cell receptor/T3 proteins, but are critically involved in the physiologic activation of T cells possibly in transmembrane signaling through surface receptors. This project proposal outlines a detailed investigation of the structure and function of TAP and TAPa on transformed (hybridoma) T cell clones, with particular emphasis on mutants, as well as on heterogeneous lymphocyte populations. The proposed investigations will cover the following aspects of these molecules: 1). The precise physiologic role of these molecules on lymphocytes and their mechanism of action. 2). The physical and functional relationship of these molecules to other T cell membrane structures, including the T cell receptor. 3). Their protein structure including amino acid sequence. 4). The molecular cloning of the corresponding cDNA and genomic sequences for characterization and their subsequent application to study gene organization, expression and function.
| McGrew, J T; Rock, K L (1991) Stimulation of human Jurkat cells by monoclonal antibody crosslinking of transfected-Ly-6A.2 (TAP) molecules. Cell Immunol 137:118-26 |
| McGrew, J T; Rock, K L (1991) Isolation, expression, and sequence of the TAP/Ly-6A.2 chromosomal gene. J Immunol 146:3633-8 |
| Pinto, V B; Rock, K L (1991) Characterization of the proliferative response of a CD4-8- thymic T lymphoma cell line to stimulation by thymic cellular elements. J Immunol 147:42-9 |
| Bamezai, A; Goldmacher, V; Reiser, H et al. (1989) Internalization of phosphatidylinositol-anchored lymphocyte proteins. I. Documentation and potential significance for T cell stimulation. J Immunol 143:3107-16 |
