Crystal structure of the complex between human CD8 alpha alpha and HLA-A2
Crystal structure of the complex between human CD8 alpha alpha and HLA-A2
复制标题
DOI：
10.1038/42523
复制
发表时间：
1997-06-05
期刊：
影响因子：
64.8
通讯作者：
Jakobsen, BK
中科院分区：
文献类型：
--
作者：
Gao, GF;Tormo, J;Jakobsen, BK
二聚体细胞表面糖蛋白CD8对胸腺细胞毒性T细胞的阳性选择至关重要(1)。同源二聚体CD8α或异二聚体αβ通过与I类分子(2)结合，稳定T细胞抗原受体(TCR)与主要组织相容性复合体(MHC)I类/肽的相互作用。在这里，我们报道了CD8α与人MHC分子HLA-A2之间的化合物的2.7埃分辨率的晶体结构，它与多肽有关。CD8α结合一个HLA-A2/多肽分子，与HLA-A2的α2和α3结构域结合，并与β(2)-微球蛋白接触。α3结构域(残基223-229)的柔性环在两个CD8亚单位的互补决定区(CDR)样环之间以抗体-抗原相互作用的经典方式被抑制，排除了第二个MHC分子的结合。α3结构域的位置与未复合的HLA-A2中的位置不同(参考文献3，4)，与TCR/Tax/HLA-A2复合体中的位置最相似(5)，但构象没有变化到用于识别TCR的MHC/肽表面。尽管α3的这些变化可能提供了亲和力的协同调节，但CD8与MHC的结合显然与CD8对TCR-肽-MHC相互作用的亲和力贡献是一致的。
The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus(1). The homodimer CD8 alpha alpha or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor(TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule(2). Here we report the crystal structure at 2.7 Angstrom resolution of a complex between CD8 alpha alpha and the human MHC molecule HLA-A2, which is associated with peptide. CD8 alpha alpha binds one HLA-A2/ peptide molecule, interfacing with the alpha 2 and alpha 3 domains of HLA-A2 and also contacting beta(2)-microglobulin. A flexible loop of the alpha 3 domain (residues 223-229) is damped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha 3 domain is different from that in uncomplexed HLA-A2 (refs 3, 4), being most similar to that in the TCR/Tax/HLA-A2 complex(5), but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha 3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions.