Zajonc Dirk M, Crispin M D Max, Bowden Thomas A, Young David C, Cheng Tan-Yun, Hu Jingdan, Costello Catherine E, Rudd Pauline M, Dwek Raymond A, Miller Marvin J, Brenner Michael B, Moody D Branch, Wilson Ian A
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Immunity. 2005 Feb;22(2):209-19. doi: 10.1016/j.immuni.2004.12.009.
CD1a is expressed on Langerhans cells (LCs) and dendritic cells (DCs), where it mediates T cell recognition of glycolipid and lipopeptide antigens that contain either one or two alkyl chains. We demonstrate here that CD1a-restricted T cells can discriminate the peptide component of didehydroxymycobactin lipopeptides. Structure analysis of CD1a cocrystallized with a synthetic mycobactin lipopeptide at 2.8 A resolution further reveals that the single alkyl chain is inserted deep within the A' pocket of the groove, whereas its two peptidic branches protrude along the F' pocket to the outer, alpha-helical surface of CD1a for recognition by the TCR. Remarkably, the cyclized lysine branch of the peptide moiety lies in the shallow F' pocket in a conformation that closely mimics that of the alkyl chain in the CD1a-sulfatide structure. Thus, this structural study illustrates how a single chain lipid can be presented by CD1 and that the peptide moiety of the lipopeptide is recognized by the TCR.
CD1a在朗格汉斯细胞（LCs）和树突状细胞（DCs）上表达，在这些细胞中，它介导T细胞对含有一条或两条烷基链的糖脂和脂肽抗原的识别。我们在此证明，受CD1a限制的T细胞能够区分二脱氢分枝杆菌脂肽的肽成分。以2.8埃分辨率对与合成分枝杆菌脂肽共结晶的CD1a进行结构分析，进一步揭示单烷基链深深插入凹槽的A'口袋内，而其两个肽分支沿着F'口袋伸向CD1a的外部α螺旋表面，以供TCR识别。值得注意的是，肽部分的环化赖氨酸分支以一种紧密模仿CD1a - 硫苷脂结构中烷基链构象的形式位于浅F'口袋中。因此，这项结构研究阐明了CD1如何呈递单链脂质以及脂肽的肽部分如何被TCR识别。
