αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands
αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands
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DOI：
10.1038/ni.3098
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发表时间：
2015-03-01
影响因子：
30.5
通讯作者：
Rossjohn, Jamie
中科院分区：
文献类型：
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作者：
Birkinshaw, Richard W.;Pellicci, Daniel G.;Rossjohn, Jamie
ab T细胞介导的免疫中的中心范例是ab T细胞抗原受体（TCR）对抗原和抗原呈递分子的同时共识别。CD 1a提供了广泛的基于脂质的抗原库。我们发现，一个典型的自身反应性TCR结合CD 1a时，它提出了一系列允许的内源性配体，而其他脂质配体是nonpermissive的TCR结合。两种TCR-CD 1a-脂质复合物的结构显示TCR以排除与允许配体直接接触的方式停靠在CD 1a的A'屋顶上。非允许配体通过破坏TCR-CD 1a接触区间接抑制TCR结合。TCR对CD 1a的排他性识别代表了一种以前未知的机制，其中ab T细胞间接感知与抗原呈递分子结合的自身抗原。
A central paradigm in ab T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the ab T cell antigen receptor (TCR). CD1a presents a broad repertoire of lipid-based antigens. We found that a prototypical autoreactive TCR bound CD1a when it was presenting a series of permissive endogenous ligands, while other lipid ligands were nonpermissive to TCR binding. The structures of two TCR-CD1a-lipid complexes showed that the TCR docked over the A' roof of CD1a in a manner that precluded direct contact with permissive ligands. Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR-CD1a contact zone. The exclusive recognition of CD1a by the TCR represents a previously unknown mechanism whereby ab T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.