Archbold Julia K, Macdonald Whitney A, Burrows Scott R, Rossjohn Jamie, McCluskey James
Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
Trends Immunol. 2008 May;29(5):220-6. doi: 10.1016/j.it.2008.02.005. Epub 2008 Apr 18.
T cells bearing alphabeta T-cell receptors (TCRs) are selected by a subset of peptide-laden major histocompatibility (pMHC) molecules in the thymus and in the periphery and therefore are restricted to recognising host or 'self' MHC molecules. Nevertheless, T cells are inherently cross-reactive and often react with 'foreign' allogeneic MHC molecules (direct T-cell alloreactivity), manifested clinically as organ transplant rejection. Although the basis of T-cell alloreactivity has remained a puzzle to immunologists for decades, studies on alloreactive TCRs have begun to shed light on the basic mechanisms underpinning this 'mistaken identity'. Here we review recent advances in the field, focusing on structural and cellular studies, showing that alloreactivity may sometimes result from cross-reactivity without molecular mimicry and at other times may result directly from TCR interactions with allogeneic pMHC surfaces that mimic the cognate ligand.
携带αβ T细胞受体（TCR）的T细胞在胸腺和外周被一类负载肽的主要组织相容性（pMHC）分子所选择，因此局限于识别宿主或“自身”MHC分子。然而，T细胞具有内在的交叉反应性，常常与“外来的”同种异体MHC分子发生反应（直接T细胞同种异体反应性），在临床上表现为器官移植排斥反应。尽管几十年来T细胞同种异体反应性的基础一直是免疫学家们的难题，但对同种异体反应性TCR的研究已开始揭示支撑这种“错误识别”的基本机制。在此，我们综述该领域的最新进展，重点关注结构和细胞研究，结果表明同种异体反应性有时可能源于无分子模拟的交叉反应性，而在其他时候可能直接源于TCR与模拟同源配体的同种异体pMHC表面的相互作用。
