Huseby Eric S, Crawford Frances, White Janice, Kappler John, Marrack Philippa
Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11565-70. doi: 10.1073/pnas.1934636100. Epub 2003 Sep 22.
The T cell alphabeta receptor (TCR) recognizes foreign peptide antigens bound to proteins encoded in the MHC. The MHC portion of this complex contributes much to the footprint of the TCR on the ligand, yet T cells are usually very specific for individual foreign peptides. Here, we show that the development of peptide-specific T cells is not intrinsic to thymocytes that undergo thymic-positive selection but is an outcome of eliminating, through negative selection, thymocytes bearing TCRs with extensive peptide cross-reactivity. Hence, thymic-negative selection imposes peptide specificity on the mature T cell repertoire.
T细胞αβ受体(TCR)识别与MHC中编码的蛋白质结合的外来肽抗原。该复合物中的MHC部分对TCR在配体上的印记有很大贡献,但T细胞通常对单个外来肽具有高度特异性。在这里,我们表明,肽特异性T细胞的发育并非经历胸腺阳性选择的胸腺细胞所固有,而是通过阴性选择消除携带具有广泛肽交叉反应性的TCR的胸腺细胞的结果。因此,胸腺阴性选择赋予成熟T细胞库肽特异性。