The Role of Lck/CD8 Association in Negatively Regulating T cell Activation

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This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unorthodox antigen recognition. Thus, the proposal will significantly advance our understanding of, and establish new paradigms around, the regulation of T cell activation. Expected long term benefits outside the scope of this proposal include improved immunotherapies and vaccines designed to elicit or suppress T cell responses.