Berg R E, Princiotta M F, Irion S, Moticka J A, Dahl K R, Staerz U D
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Immunity. 1999 Jul;11(1):33-43. doi: 10.1016/s1074-7613(00)80079-5.
Thymocytes are positively selected for alphabeta T cell antigen receptors (TCR) that recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules. MHC bound peptides participate in positive selection; however, their role has remained controversial. A TCR transgenic mouse was established using a TCR restricted to the MHC class Ib molecule, H2-M3. Having defined H2-M3 as the positively selecting MHC molecule, the severely limited number of H2-M3 binding peptides allowed us to characterize an NADH dehydrogenase subunit 1 (ND1)-derived peptide as the physiological ligand of positive selection. This peptide bears no apparent sequence homology to the cognate peptide, is expressed ubiquitously, and yet does not interfere with peripheral T cells. Our studies also suggest that positive selection becomes promiscuous at high epitope densities.
胸腺细胞会被针对αβ T细胞抗原受体（TCR）进行阳性选择，该受体可与自身主要组织相容性复合体（MHC）分子结合识别抗原。MHC结合肽参与阳性选择；然而，它们的作用一直存在争议。利用一种受限于MHC Ib类分子H2-M3的TCR建立了一只TCR转基因小鼠。在确定H2-M3为进行阳性选择的MHC分子后，数量极为有限的H2-M3结合肽使我们能够将一种烟酰胺腺嘌呤二核苷酸脱氢酶亚基1（ND1）衍生肽鉴定为阳性选择的生理配体。该肽与同源肽没有明显的序列同源性，广泛表达，但不干扰外周T细胞。我们的研究还表明，在高表位密度下阳性选择会变得杂乱。
