Antigen presentation to T cells in nonlymphoid tissue

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DESCRIPTION (provided by applicant): It has been well established that antigen presentation in secondary lymphoid organs is essential for the initiation of an antigen specific adaptive immune response. The primary phase of this response consists of antigen presentation by dendritic cells in the context of MHC II where it is then recognized by CD4+ T cells which in turn can become activated. Activated effector CD4+ T cells migrate back into sites of antigen deposition where they can remain for weeks. This proposal seeks to determine the role of antigen presentation in nonlymphoid tissues with respect to its effect on CD4+ T cells. While we expect that the inflammatory milieu in the tissue initiates the entry of effector T cells equally, we hypothesize that in order for maximal accumulation, sequestration, and sustained activation to occur, antigen-specific T cells must recognize cognate antigen in the context of MHC II at the actual site of antigen deposition. Our hypothesis is that while dendritic cells activate T cells in the lymph nodes, macrophages in the tissue is responsible for antigen presentation at the site of antigen deposition and for the sustained activation and retention of CD4+ T cells.