Biddison William E, Turner Richard V, Gagnon Susan J, Lev Avital, Cohen Cyril J, Reiter Yoram
Molecular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2003 Sep 15;171(6):3064-74. doi: 10.4049/jimmunol.171.6.3064.
Both TCRs and Ab molecules are capable of MHC-restricted recognition of peptide/MHC complexes. However, such MHC restriction is the predominant mode of recognition by T cells, but is extremely rare for B cells. The present study asks whether the dichotomy in Ag recognition modes of T and B cells could be due to fundamental differences in the methods by which TCRs and Abs recognize peptide/MHC complexes. We have compared MHC and peptide recognition by panels of CTL lines specific for the Tax and M1 peptides presented by HLA-A2 plus Tax and M1 peptide/HLA-A2-specific human Fabs that were selected from a naive phage display library. Collectively, the results indicate both striking similarities and important differences between Fab and TCR recognition of MHC and peptide components of the Tax and M1/HLA-A2 complexes. These findings suggest that these two classes of immunoreceptors have solved the problem of specific recognition of peptide/MHC complexes by nonidentical mechanisms. This conclusion is important in part because it indicates that Ab engineering approaches could produce second-generation Ab molecules that more closely mimic TCR fine specificity. Such efforts may produce more efficacious diagnostic and therapeutic agents.
T细胞受体（TCRs）和抗体（Ab）分子都能够对肽/MHC复合物进行MHC限制识别。然而，这种MHC限制是T细胞识别的主要模式，但对B细胞来说极为罕见。本研究探讨T细胞和B细胞在抗原识别模式上的二分法是否可能源于TCRs和Abs识别肽/MHC复合物方式的根本差异。我们比较了针对由HLA - A2递呈的Tax和M1肽的CTL系组以及从天然噬菌体展示文库中筛选出的Tax和M1肽/HLA - A2特异性人Fab对MHC和肽的识别。总体而言，结果表明Fab和TCR对Tax和M1/HLA - A2复合物的MHC和肽成分的识别既有显著相似性也有重要差异。这些发现表明这两类免疫受体通过不同机制解决了肽/MHC复合物的特异性识别问题。这一结论部分很重要，因为它表明抗体工程方法可以产生更紧密模拟TCR精细特异性的第二代抗体分子。此类努力可能会产生更有效的诊断和治疗药物。
