Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact
Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact
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DOI：
10.1073/pnas.250470797
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发表时间：
2000-12-05
影响因子：
11.1
通讯作者：
Sasazuki, T
中科院分区：
文献类型：
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作者：
Fukui, Y;Oono, T;Sasazuki, T
胸腺中的T细胞分化是通过α β T细胞受体（TCR）与结合至自身主要组织相容性复合物分子的自身肽的相互作用由正选择驱动的，然而肽序列对该过程的影响仍然未知。为了解决这个问题，我们比较了两组小鼠系之间的CD 4（+）T细胞分化，其中MHC II类I-Ab分子被E α链衍生肽（pE α）或其变体p60 K占据，在TCR接触的P5残基处有一个氨基酸从亮氨酸取代为赖氨酸。在这里，我们表明，尽管I-A（B）-肽复合物在胸腺中的表达相当，但这种从亮氨酸到赖氨酸的取代影响了阳性选择的效率，导致极少数的CD 4（+）T细胞被选择在I-A（B）-，60 K复合物上成熟。此外，我们发现，虽然I-A（B）-，E α复合物选择不同的T细胞，但由I-A（B）-p60 K复合物形成的T细胞库明显受到限制。因此，我们的研究结果表明，积极的选择是特异性的和简并的，这取决于在TCR接触的选择自我肽的氨基酸残基。
T cell differentiation in the thymus is driven by positive selection through the interaction of alpha beta T cell receptors (TCRs) with self-peptides bound to self-major histocompatibility complex molecules, yet the influence of the peptide sequence on this process remains unknown. To address this issue, we have compared CD4(+) T cell differentiation between two sets of mouse lines in which MHC class II I-Ab molecules are occupied with either E alpha chain-derived peptide (pE alpha) or its variant, p60K, with one amino acid substitution from leucine to lysine at P5 residue of TCR contacts. Here, we show that despite the comparable expression of I-A(b)-peptide complex in the thymus, this substitution from leucine to lysine affects efficiency of positive selection, resulting in extremely small numbers of CD4(+) T cells to be selected to mature on I-A(b)-,60K complex. Furthermore, we show that, although I-A(b)-,E alpha complex selects diverse T cells, T cell repertoire shaped by I-A(b)-p60K complex is markedly constrained. Our findings thus suggest that positive selection is both specific and degenerate, depending on the amino acid residues at TCR contacts of the selecting self-peptides.