Gagnon Susan J, Wang Zichun, Turner Richard, Damirjian Marale, Biddison William E
Molecular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2003 Sep 1;171(5):2233-41. doi: 10.4049/jimmunol.171.5.2233.
T cell recognition by peptide-specific alphabeta TCRs involves not only recognition of the peptide, but also recognition of multiple molecular features on the surface of the MHC molecule to which the peptide has been bound. We have previously shown that TCRs that are specific for five different peptides presented by HLA-A2 recognize similar molecular features on the surface of the alpha1 and alpha2 helices of the HLA-A2 molecule. We next asked whether these same molecular features of the HLA-A2 molecule would be recognized by hapten-specific HLA-A2-restricted TCRs, given that hapten-specific T cells frequently show reduced MHC dependence/restriction. The results show that a panel of CD8+ CTL that are specific for the hapten DNP bound to two different peptides presented by HLA-A2 do the following: 1) show stringent MHC restriction, and 2) are largely affected by the same mutations on the HLA-A2 molecule that affected recognition by peptide-specific CTL. A small subset of this panel of CD8+ CTL can recognize a mutant HLA-A2 molecule in the absence of hapten. These data suggest that TCR recognition of a divergent repertoire of ligands presented by HLA-A2 is largely dependent upon common structural elements in the central portion of the peptide-binding site.
肽特异性αβTCR对T细胞的识别不仅涉及对肽的识别，还涉及对与该肽结合的MHC分子表面多种分子特征的识别。我们之前已经表明，对HLA - A2呈递的五种不同肽具有特异性的TCR识别HLA - A2分子α1和α2螺旋表面的相似分子特征。接下来我们想问，鉴于半抗原特异性T细胞经常表现出对MHC依赖性/限制性的降低，HLA - A2分子的这些相同分子特征是否会被半抗原特异性HLA - A2限制性TCR识别。结果表明，一组对与HLA - A2呈递的两种不同肽结合的半抗原DNP具有特异性的CD8⁺CTL表现如下：1）表现出严格的MHC限制性，并且2）在很大程度上受到HLA - A2分子上相同突变的影响，这些突变影响了肽特异性CTL的识别。该组CD8⁺CTL中的一小部分在没有半抗原的情况下可以识别突变的HLA - A2分子。这些数据表明，TCR对HLA - A2呈递的多种不同配体的识别在很大程度上取决于肽结合位点中央部分的共同结构元件。
