Crossreactive T cells spotlight the germline rules for αβ T cell-receptor interactions with MHC molecules
Crossreactive T cells spotlight the germline rules for αβ T cell-receptor interactions with MHC molecules
复制标题
DOI：
10.1016/j.immuni.2008.01.008
复制
发表时间：
2008-03-01
期刊：
影响因子：
32.4
通讯作者：
Kappler, John W.
中科院分区：
文献类型：
--
作者：
Dai, Shaodong;Huseby, Eric S.;Kappler, John W.
为了测试在有限负选择期间产生的高度交叉反应性α β T细胞受体（TCR）是否最好地说明TCR与主要组织相容性复合体（MHC）分子之间的进化保守的相互作用，我们解析了与相同MHC II肽（IA（B）-3 K）结合的三种TCR的结构。TCR对IA（B）-3K具有相似的亲和力，但与其他肽和MHC的交叉反应性从非交叉反应性到极端交叉反应性不等。交叉反应性与缩小，越来越疏水的TCR-配体界面，涉及更少的TCR氨基酸。少数CDR 1和CDR 2氨基酸占主导地位的最交叉反应性的TCR界面与MHC，包括V β 8 48 Y和54 E和V α 4 29 Y，安排强加熟悉的对角取向的TCR对MHC。这些相互作用有助于其他TCR使用相关的V区结合MHC，但通常不占主导地位。这些数据表明，交叉反应性TCR可以突出TCR-MHC相互作用的进化保守特征，并且这些相互作用将TCR的对角对接强加于MHC。
To test whether highly crossreactive alpha beta T cell receptors (TCRs) produced during limited negative selection best illustrate evolutionarily conserved interactions between TCR and major histocompatibility complex (MHC) molecules, we solved the structures of three TCRs bound to the same MHC II peptide(IA(b)- 3K). The TCRs had similar affinities for IA(b)-3K but varied from noncrossreactive to extremely crossreactive with other peptides and MHCs. Crossreactivity correlated with a shrinking, increasingly hydrophobic TCR-ligand interface, involving fewer TCR amino acids. A few CDR1 and CDR2 amino acids dominated the most crossreactive TCR interface with MHC, including V beta 8 48Y and 54E and V alpha 4 29Y, arranged to impose the familiar diagonal orientation of TCR on MHC. These interactions contribute to MHC binding by other TCRs using related V regions, but not usually so dominantly. These data show that crossreactive TCRs can spotlight the evolutionarily conserved features of TCR-MHC interactions and that these interactions impose the diagonal docking of TCRs on MHC.