A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition
A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition
复制标题
DOI：
10.1073/pnas.0403371101
复制
发表时间：
2004-09-07
影响因子：
11.1
通讯作者：
Stern, LJ
中科院分区：
文献类型：
--
作者：
Zavala-Ruiz, Z;Strug, I;Stern, LJ
T细胞通常通过与MHC肽结合沟中容纳的7至9个残基序列内或紧邻其侧翼的残基接触来识别与MHC蛋白结合的肽抗原。然而，一些T细胞需要该区域外的肽残基来激活，其结构基础尚不清楚。在这里，我们研究了一种HIV GAG特异性T细胞克隆，它需要一种异常长的肽抗原来激活。与HLA-DR 1结合的最低抗原性16聚体的晶体结构显示，肽C末端区域在离开结合位点时急剧弯曲成发夹状，将肽残基定向在MHC结合区域外的位置以与T细胞受体相互作用。肽截短和取代研究表明，发夹转角和极端的C-末端残基都是T细胞活化所必需的。这些结果证明了一种以前未被认识到的MHC-肽-T细胞受体相互作用模式。
T cells generally recognize peptide antigens bound to MHC proteins through contacts with residues found within or immediately flanking the seven- to nine-residue sequence accommodated in the MHC peptide-binding groove. However, some T cells require peptide residues outside this region for activation, the structural basis for which is unknown. Here, we have investigated a HIV Gag-specific T cell clone that requires an unusually long peptide antigen for activation. The crystal structure of a minimally antigenic 16-mer bound to HLA-DR1 shows that the peptide C-terminal region bends sharply into a hairpin turn as it exits the binding site, orienting peptide residues outside the MHC-binding region in position to interact with a T cell receptor. Peptide truncation and substitution studies show that both the hairpin turn and the extreme C-terminal residues are required for T cell activation. These results demonstrate a previously unrecognized mode of MHC-peptide-T cell receptor interaction.