Salzmann M, Bachmann M F
Basel Institute of Immunology, Switzerland.
Mol Immunol. 1998 Apr;35(5):271-7. doi: 10.1016/s0161-5890(98)00035-2.
T cell responses are highly specific and T cell receptors (TCRs) can recognise subtle differences in major histocompatibility complex (MHC)-peptide complexes. While nominal peptide antigens usually act as full agonists that trigger the whole spectrum of T cell responses, some peptides exhibiting mutations at the TCR-MHC/peptide contact site stimulate only a fraction of T cell responses (partial agonists) or may even inhibit T cell activation by full agonists (antagonist). The present study analyses mathematically the role of TCR-dimerization for T cell antagonism and T cell specificity in general. It demonstrates that T cell antagonists can effectively inhibit TCR-dimerization and that this mechanism can sufficiently explain all aspects of T cell antagonism. The kinetic model of T cell activation proposes that increasing the time required for effective TCR-signaling is the most effective mechanism to increase the discriminatory capacity of TCRs. Our results indicate that TCR-oligomerization is an alternative and efficient mechanism to ensure T cell specificity.
T细胞反应具有高度特异性，T细胞受体（TCR）能够识别主要组织相容性复合体（MHC）-肽复合物中的细微差异。虽然名义肽抗原通常作为完全激动剂触发整个T细胞反应谱，但一些在TCR-MHC/肽接触位点表现出突变的肽仅刺激一部分T细胞反应（部分激动剂），甚至可能抑制完全激动剂对T细胞的激活（拮抗剂）。本研究从数学角度分析了TCR二聚化在一般T细胞拮抗作用和T细胞特异性中的作用。结果表明，T细胞拮抗剂可有效抑制TCR二聚化，且该机制能够充分解释T细胞拮抗作用的各个方面。T细胞激活的动力学模型提出，增加有效TCR信号传导所需的时间是提高TCR辨别能力的最有效机制。我们的结果表明，TCR寡聚化是确保T细胞特异性的一种替代且有效的机制。
