Antigen presentation to T cells in nonlymphoid tissue

描述（由申请人提供）：已经证实，抗原在次级淋巴器官的呈递对于抗原特异性适应性免疫反应的启动是必不可少的。这种反应的初级阶段包括树突状细胞在MHC II环境下的抗原呈递，然后被CD4+ T细胞识别，CD4+ T细胞反过来被激活。活化的效应CD4+ T细胞迁移回抗原沉积的部位，在那里它们可以停留数周。本研究旨在确定抗原呈递在非淋巴组织中的作用及其对CD4+ T细胞的影响。虽然我们预计组织中的炎症环境同样会启动效应T细胞的进入，但我们假设，为了实现最大的积累、隔离和持续激活，抗原特异性T细胞必须在抗原沉积的实际位置识别MHC II背景下的同源抗原。我们的假设是，当树突状细胞激活淋巴结中的T细胞时，组织中的巨噬细胞负责抗原沉积部位的抗原呈递以及CD4+ T细胞的持续激活和保留。

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.