Contribution of TCR-β locus and HLA to the shape of the mature human Vβ repertoire
Contribution of TCR-β locus and HLA to the shape of the mature human Vβ repertoire
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DOI：
10.4049/jimmunol.180.10.6484
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发表时间：
2008-05-15
影响因子：
4.4
通讯作者：
Barrett, A. John
中科院分区：
文献类型：
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作者：
Melenhorst, J. Joseph;Lay, Matthew D. H.;Barrett, A. John
在胸腺选择中存活的T细胞表达多种独特的异二聚体α β TCR，其介导肽-MHC Ag识别。表达特定V β蛋白的总T细胞库的比例可以由多种因素决定：1）对使用特定V β基因的种系偏好; 2）对不同V β基因表达的等位基因效应;和3）HLA对不同V β基因表达的效应（通过胸腺选择和/或外周机制起作用）。在这项研究中，我们发现新生儿和成人供体中人CD 4（+）和CD 8（+）T细胞的V β使用在无关个体之间高度相关，这表明观察到的V β表达模式的很大一部分是由TCR-β基因座的内在因素决定的。相同TCR等位基因的存在（在个体内）导致CD 4（+）和CD 8（+）T细胞之间关于V β表达的显著更好的相关性;然而，这些影响相对较小。个体之间HLA等位基因的共享也导致他们的V β表达模式之间的相关性增加，尽管这没有达到统计学显著性。因此，我们得出结论，CD 4（+）和CD 8（+）T细胞之间V β表达模式的相关性可以主要由生殖系TCR β基因座因素解释，而不是TCR β等位基因或HLA效应。
T cells that survive thymic selection express a diverse array of unique heterodimeric alpha beta TCRs that mediate peptide-MHC Ag recognition. The proportion of the total T cell repertoire that expresses a particular V beta protein may be determined by a variety of factors: 1) germline preference for use of particular V beta genes; 2) allelic effects on the expression of different V beta genes; and 3) HLA effects on the expression of different V beta genes (acting via thymic selection and/or peripheral mechanisms). In this study, we show that V beta usage by human CD4(+) and CD8(+) T cells in neonatal and adult donors is highly correlated between unrelated individuals, suggesting that a large proportion of the observed pattern of V beta expression is determined by factors intrinsic to the TCR-beta locus. The presence of identical TCR alleles (within an individual) leads to a significantly better correlation between CD4(+) and CD8(+) T cells with respect to V beta expression; these effects are, however, relatively minor. The sharing of HLA alleles between individuals also leads to an increased correlation between their V beta expression patterns, although this did not reach statistical significance. We therefore conclude that the correlation in V beta expression patterns between CD4(+) and CD8(+) T cells can be explained predominantly by germline TCR-beta locus factors and not TCR-beta allelic or HLA effects.