Holler Phillip D, Chlewicki Lukasz K, Kranz David M
Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
Nat Immunol. 2003 Jan;4(1):55-62. doi: 10.1038/ni863. Epub 2002 Dec 9.
T cells with high-affinity T cell receptors (TCRs) for a foreign peptide-major histocompatibility complex (pMHC) appear to be negatively selected, even though they have never seen the foreign antigen. To examine how this process operates, we used in vitro yeast display to isolate high-affinity TCRs from the T cell clone 2C. The TCRs showed fast on-rates, which were consistent with reduced CDR (complementarity determining region) flexibility, and cross-reactivity with other cognate pMHCs. T cell hybridomas transfected with a high-affinity TCR were stimulated by endogenous self-pMHC, which suggested that T cells bearing the TCR would be negatively selected. The immune system appears to maintain a repertoire of flexible, low-affinity TCRs at the expense of more effective high-affinity TCRs.
对于外来肽 - 主要组织相容性复合体（pMHC）具有高亲和力T细胞受体（TCR）的T细胞，即便从未接触过外来抗原，似乎也会被阴性选择。为了研究这一过程是如何发生的，我们利用体外酵母展示技术从T细胞克隆2C中分离出高亲和力TCR。这些TCR显示出快速的结合速率，这与互补决定区（CDR）灵活性降低以及与其他同源pMHC的交叉反应性相一致。转染了高亲和力TCR的T细胞杂交瘤受到内源性自身pMHC的刺激，这表明携带该TCR的T细胞会被阴性选择。免疫系统似乎以牺牲更有效的高亲和力TCR为代价，维持着一套灵活的低亲和力TCR库。
