Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, USA.
Nat Immunol. 2014 Mar;15(3):266-74. doi: 10.1038/ni.2822. Epub 2014 Feb 2.
Interactions of T cell antigen receptors (TCRs) with complexes of self peptide and major histocompatibility complex (MHC) are crucial to T cell development, but their role in peripheral T cell responses remains unclear. Specific and nonspecific stimulation of LLO56 and LLO118 T cells, which transgenically express a TCR specific for the same Listeria monocytogenes epitope, elicited distinct interleukin 2 (IL-2) and phosphorylated kinase Erk responses, the strength of which was set in the thymus and maintained in the periphery in proportion to the avidity of the binding of the TCR to the self peptide-MHC complex. Deprivation of self peptide-MHC substantially compromised the population expansion of LLO56 T cells in response to L. monocytogenes in vivo. Despite their very different self-reactivity, LLO56 T cells and LLO118 T cells bound cognate peptide-MHC with an identical affinity, which challenges associations made between these parameters. Our findings highlight a crucial role for selecting ligands encountered during thymic 'education' in determining the intrinsic functionality of CD4+ T cells.
T 细胞抗原受体（TCRs）与自身肽和主要组织相容性复合体（MHC）复合物的相互作用对 T 细胞的发育至关重要，但它们在周围 T 细胞反应中的作用仍不清楚。转染表达针对李斯特菌单核细胞增生症相同表位的 TCR 的 LLO56 和 LLO118 T 细胞的特异性和非特异性刺激，引发了不同的白细胞介素 2（IL-2）和磷酸化激酶 Erk 反应，其强度在胸腺中确定，并在外周保持与 TCR 与自身肽-MHC 复合物的结合亲和力成比例。剥夺自身肽-MHC 大大损害了 LLO56 T 细胞对李斯特菌单核细胞增生症体内的群体扩张。尽管它们具有非常不同的自身反应性，但 LLO56 T 细胞和 LLO118 T 细胞与同源肽-MHC 的结合亲和力相同，这对这些参数之间的关联提出了挑战。我们的发现强调了在胸腺“教育”过程中遇到的配体选择在决定 CD4+ T 细胞的固有功能方面的关键作用。
