Department of Microbiology and Immunology, University of Melbourne, Parkville, Melbourne, VIC, Australia.
Eur J Immunol. 2010 Mar;40(3):849-58. doi: 10.1002/eji.200939918.
TCR repertoire diversity is important for the protective efficacy of CD8(+) T cells, limiting viral escape and cross-reactivity between unrelated epitopes. The exact mechanism for selection of restricted versus diverse TCR repertoires is far from clear, although one thought is that the epitopes resembling self-peptides might select a limited array of TCR due to the deletion of autoreactive TCR. The molecule Aire promotes the expression of tissue-specific Ag on thymic medullary epithelial cells and the deletion of autoreactive cells, and in the absence of Aire autoreactive cells persist. However, the contribution of Aire-dependent peptides to the selection of the Ag-specific TCR repertoire remains unknown. In this study, we dissect restricted (D(b)NP(366)%(+)CD8(+)) and diverse (D(b)PA(224)%(+)CD8(+), K(d)NP(147)%(+)CD8(+)) TCR repertoires responding to three influenza-derived peptides in Aire-deficient mice on both B6 and BALB/c backgrounds. Our study shows that the number, qualitative characteristics and TCR repertoires of all influenza-specific, D(b)NP(366)%(+)CD8(+), D(b)PA(224)%(+)CD8(+) and K(d)NP(147)%(+)CD8(+) T cells are not significantly altered in the absence of Aire. This provides the first demonstration that the selection of an Ag-specific T-cell repertoire is not significantly perturbed in the absence of Aire.
T 细胞受体（TCR） repertoire 多样性对于 CD8(+) T 细胞的保护效力很重要，它限制了病毒逃逸和不相关表位之间的交叉反应。选择受限或多样化 TCR repertoire 的精确机制尚不清楚，尽管有一种观点认为，类似于自身肽的表位可能由于自身反应性 TCR 的缺失而选择有限的 TCR 阵列。Aire 分子促进组织特异性抗原在胸腺髓质上皮细胞上的表达和自身反应性细胞的缺失，如果没有 Aire，自身反应性细胞则持续存在。然而，Aire 依赖性肽对抗原特异性 TCR repertoire 选择的贡献仍然未知。在这项研究中，我们在 B6 和 BALB/c 背景下的 Aire 缺陷小鼠中，对三种流感衍生肽的反应性受限（D(b)NP(366)%(+)CD8(+））和多样化（D(b)PA(224)%(+)CD8(+）、K(d)NP(147)%(+)CD8(+））TCR repertoire 进行了剖析。我们的研究表明，在没有 Aire 的情况下，所有流感特异性、D(b)NP(366)%(+)CD8(+）、D(b)PA(224)%(+)CD8(+）和 K(d)NP(147)%(+)CD8(+）T 细胞的数量、定性特征和 TCR repertoire 都没有明显改变。这首次证明了在没有 Aire 的情况下，抗原特异性 T 细胞 repertoire 的选择没有受到明显干扰。
