Cemerski Saso, Das Jayajit, Locasale Jason, Arnold Phoebe, Giurisato Emanuele, Markiewicz Mary A, Fremont Daved, Allen Paul M, Chakraborty Arup K, Shaw Andrey S
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Immunity. 2007 Mar;26(3):345-55. doi: 10.1016/j.immuni.2007.01.013. Epub 2007 Mar 8.
T cell activation is predicated on the interaction between the T cell receptor and peptide-major histocompatibility (pMHC) ligands. The factors that determine the stimulatory potency of a pMHC molecule remain unclear. We describe results showing that a peptide exhibiting many hallmarks of a weak agonist stimulates T cells to proliferate more than the wild-type agonist ligand. An in silico approach suggested that the inability to form the central supramolecular activation cluster (cSMAC) could underlie the increased proliferation. This conclusion was supported by experiments that showed that enhancing cSMAC formation reduced stimulatory capacity of the weak peptide. Our studies highlight the fact that a complex interplay of factors determines the quality of a T cell antigen.
T细胞活化取决于T细胞受体与肽-主要组织相容性复合体（pMHC）配体之间的相互作用。决定pMHC分子刺激效力的因素仍不清楚。我们描述的结果表明，一种表现出许多弱激动剂特征的肽比野生型激动剂配体更能刺激T细胞增殖。一种计算机模拟方法表明，无法形成中央超分子活化簇（cSMAC）可能是增殖增加的原因。这一结论得到了实验的支持，实验表明增强cSMAC的形成会降低弱肽的刺激能力。我们的研究强调了一个事实，即多种因素的复杂相互作用决定了T细胞抗原的质量。
