The relationship of MHC-peptide binding and T cell activation probed using chemically defined MHC class II oligomers
The relationship of MHC-peptide binding and T cell activation probed using chemically defined MHC class II oligomers
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DOI：
10.1016/s1074-7613(00)80177-6
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发表时间：
2000-03-01
期刊：
影响因子：
32.4
通讯作者：
Stern, LJ
中科院分区：
文献类型：
--
作者：
Cochran, JR;Cameron, TO;Stern, LJ
构建了一系列新型的人主要组织相容性复合体（MHC）II类蛋白HLA - DR1的化学限定可溶性寡聚体，以探究启动T细胞活化的分子需求。通过活化标记物CD69和CD25的上调以及活化T细胞受体亚基的内化来检测，发现MHC二聚体、三聚体和四聚体可刺激T细胞。单体MHC - 肽复合物可与T细胞受体结合，但不诱导活化。对于给定的受体结合量，每种寡聚体的活化程度相同，且与诱导的T细胞受体交联数量相关。这些结果表明，T细胞受体二聚体的形成或重排对于启动T细胞信号传导是必要且充分的。
A series of novel chemically defined soluble oligomers of the human MHC class II protein HLA-DR1 was constructed to probe the molecular requirements for initiation of T cell activation. MHC dimers, trimers, and tetramers stimulated T cells, as measured by upregulation of the activation markers CD69 and CD25, and by internalization of activated T cell receptor subunits. Monomeric MHC-peptide complexes engaged T cell receptors but did not induce activation. For a given amount of receptor engagement, the extent of activation was equivalent for each of the oligomers and correlated with the number of T cell receptor cross-links induced. These results suggest that formation or rearrangement of a T cell receptor dimer is necessary and sufficient for initiation of T cell signaling.