Chao Dennis L, Davenport Miles P, Forrest Stephanie, Perelson Alan S
Fred Hutchinson Cancer Research Center, Seattle, USA.
Eur J Immunol. 2005 Dec;35(12):3452-9. doi: 10.1002/eji.200535098.
Based on the results of a computational model of thymic selection, we propose a mechanism that produces the observed wide range of T cell cross-reactivity. The model suggests that the cross-reactivity of a T cell that survives thymic selection is correlated with its affinity for self peptides. In order to survive thymic selection, a T cell with low affinity for all self peptides expressed in the thymus must have high affinity for major histocompatibility complex (MHC), which makes it highly cross-reactive. A T cell with high affinity for any self peptide must have low MHC affinity to survive selection, which makes it highly specific for its cognate peptide. Our model predicts that (1) positive selection reduces by only 17% the number of T cells that can detect any given foreign peptide, even though it eliminates over 95% of pre-selection cells; (2) negative selection decreases the average cross-reactivity of the pre-selection repertoire by fivefold; and (3) T cells responding to foreign peptides similar to self peptides will have a lower average cross-reactivity than cells responding to epitopes dissimilar to self.
基于胸腺选择计算模型的结果，我们提出了一种机制，该机制能够产生所观察到的广泛的T细胞交叉反应性。该模型表明，在胸腺选择中存活下来的T细胞的交叉反应性与其对自身肽的亲和力相关。为了在胸腺选择中存活，对胸腺中表达的所有自身肽亲和力低的T细胞必须对主要组织相容性复合体（MHC）具有高亲和力，这使其具有高度交叉反应性。对任何自身肽具有高亲和力的T细胞必须具有低MHC亲和力才能在选择中存活，这使其对其同源肽具有高度特异性。我们的模型预测：（1）阳性选择仅将能够检测任何给定外来肽的T细胞数量减少17%，尽管它消除了超过95%的选择前细胞；（2）阴性选择将选择前库的平均交叉反应性降低五倍；（3）与自身肽相似的外来肽反应的T细胞的平均交叉反应性将低于与自身不同表位反应的细胞。
