Immunity against cancerous cells requires the recognition of tumor specific antigens by T lymphocytes. Although the specificity of such responses are determined, in part, by the T cell antigen receptors, the successful recognition of tumor cells requires the cooperation of other proteins on the surface of the T cell. In the studies proposed here, we will focus on one of these accessory proteins, CD2. Interactions between CD2 and its ligands CD48 and CD58 are known to enhance tumor cell recognition by both T and NK cells but the exact function of CD2 is not known. Recently, we cloned a novel protein, CD2AP, that binds to CD2 during T cell activation. This allowed us to propose that the clustering of CD2 regulates the affinity of CD2 for its ligands to facilitate recognition of target cells by T and NK cells.
In specific aim#1, we propose to determine how CD2AP is regulated and how it functions.
In specific aim #2, we propose to analyze the role of CD2 clustering in T cell activation. Lastly, we plan to study the role for CD2 in tumor immunity. The results of our work may lead to a better understanding of how tumor evade the immune system.
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