Hong S C, Waterbury G, Janeway C A
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Exp Med. 1996 Apr 1;183(4):1437-46. doi: 10.1084/jem.183.4.1437.
CD4 T cell receptors (TCRs) recognize antigenic peptides presented by self major histocompatibility complex (MHC) class II molecules as well as non-self MHC class II molecules. The TCRs can also recognize endogenous retroviral gene products and bacterial toxins known collectively as superantigens (SAGs) that act mainly on the Vbeta gene segment-encoded portion of the Vbeta domain; most SAGs also require MHC II class for presentation. We have studied the interaction of the TCR from a well-characterized CD4 T cell line with SAGs by mutational analysis of its Vbeta domain. This appears to separate viral (v)SAG from bacterial (b)SAG recognition. T cells having a TCR with glycine to valine mutation in amino acid residue 51 (G51V) in complementarity determining region 2 of the TCR Vbeta domain fail to respond the bSAGs staphylococcal enterotoxin B (SEB), SEC1, SEC2, and SEC3, whereas they retain the ability to respond to non-self MHC class II molecules and to foreign peptides presented by self MHC class II molecules. It is interesting to note that T cells expressing mutations of both G51V and G53D of V beta regain the response to SEB and partially that to SEC1, but do not respond to SEC2, and SEC3, suggesting that different bacterial SAGs are viewed differently by the same TCR. These results are surprising, because it has been generally believed that SAG recognition by T cells is mediated exclusively by hypervariable region 4 on the exposed, lateral face of the TCR Vbeta domain. Response to the vSAG Mtv-7 was generated by mutation in Vbeta residue 24 (N24H), confirming previously published data. These data show that the vSAG Mtv-7 and bSAGs are recognized by different regions of the TCR Vbeta domain. In addition, various bSAGs are recognized differently by the same TCR. Thus, these mutational data, combined with the crystal structure of the TCR beta chain, provide evidence for distinct recognition sites for vSAG and bSAG.
CD4 T细胞受体（TCR）可识别由自身主要组织相容性复合体（MHC）II类分子以及非自身MHC II类分子呈递的抗原肽。TCR还能识别内源性逆转录病毒基因产物和统称为超抗原（SAG）的细菌毒素，这些超抗原主要作用于Vβ结构域中由Vβ基因片段编码的部分；大多数超抗原还需要MHC II类分子进行呈递。我们通过对其Vβ结构域进行突变分析，研究了来自一个特征明确的CD4 T细胞系的TCR与超抗原之间的相互作用。这似乎将病毒（v）超抗原与细菌（b）超抗原的识别区分开来。在TCR Vβ结构域互补决定区2中氨基酸残基51（G51V）发生甘氨酸到缬氨酸突变的T细胞，对细菌超抗原葡萄球菌肠毒素B（SEB）、SEC1、SEC2和SEC3无反应，而它们保留了对非自身MHC II类分子以及由自身MHC II类分子呈递的外来肽作出反应的能力。有趣的是，表达Vβ的G51V和G53D双突变的T细胞恢复了对SEB的反应，并部分恢复了对SEC1的反应，但对SEC2和SEC3无反应，这表明同一TCR对不同的细菌超抗原的看待方式不同。这些结果令人惊讶，因为人们普遍认为T细胞对超抗原的识别完全由TCR Vβ结构域暴露的侧面上的高变区4介导。对病毒超抗原Mtv-7的反应是由Vβ残基24（N24H）的突变产生的，这证实了先前发表的数据。这些数据表明，病毒超抗原Mtv-7和细菌超抗原由TCR Vβ结构域的不同区域识别。此外，同一TCR对各种细菌超抗原的识别方式也不同。因此，这些突变数据与TCRβ链的晶体结构相结合，为病毒超抗原和细菌超抗原的不同识别位点提供了证据。
