Gulwani-Akolkar B, Shi B, Akolkar P N, Ito K, Bias W B, Silver J
Departments of Medicine, North Shore University Hospital, Cornell University Medical College, Manhasset, NY 11030, USA.
J Immunol. 1995 Apr 15;154(8):3843-51.
Previous studies in humans have demonstrated that HLA genes can profoundly influence the TCR V beta repertoire. To similarly assess the influence of HLA genes on the TCR V alpha segment repertoire, the V alpha repertoires of 12 individuals from three unrelated families were determined by quantitative PCR. Each family contained at least one pair of HLA-identical and -nonidentical siblings. Repertoire analysis was performed on purified CD4+ and CD8+ cells by using V alpha-specific primers. We were unable to demonstrate more similar V alpha repertoires between HLA-identical siblings than between HLA-nonidentical siblings. In contrast, when a similar analysis was performed on the same individuals for the V beta repertoire, HLA-identical siblings were found to have significantly more similar repertoires than HLA-nonidentical siblings. Furthermore, both the V alpha and V beta repertoires of monozygotic twins showed striking similarity. Despite our inability to show an influence of HLA genes on the V alpha repertoire, we did observe a very strong skewing in terms of preferential expression on CD4+ or CD8+ cells of several V alpha segments, notably TCRAV1, -2, -5, -6, -7, -11, -12, and -13. These studies suggest that HLA genes play less of a role in determining V alpha segment usage than V beta. Nevertheless, the pronounced skewing of V alpha segment expression in the CD4+ or CD8+ populations suggests some role for HLA genes in determining the V alpha TCR repertoire. Furthermore, the striking similarity of V alpha repertoires of identical twins suggests a major role for non-HLA genes in determining the V alpha repertoire.
先前针对人类的研究表明，HLA基因可深刻影响TCR Vβ库。为了类似地评估HLA基因对TCR Vα片段库的影响，通过定量PCR测定了来自三个无亲缘关系家庭的12名个体的Vα库。每个家庭至少包含一对HLA相同和不同的兄弟姐妹。通过使用Vα特异性引物对纯化的CD4 +和CD8 +细胞进行库分析。我们无法证明HLA相同的兄弟姐妹之间的Vα库比HLA不同的兄弟姐妹之间更相似。相比之下，当对同一批个体的Vβ库进行类似分析时，发现HLA相同的兄弟姐妹的库比HLA不同的兄弟姐妹的库明显更相似。此外，同卵双胞胎的Vα和Vβ库都显示出惊人的相似性。尽管我们无法证明HLA基因对Vα库有影响，但我们确实观察到几个Vα片段在CD4 +或CD8 +细胞上优先表达方面存在非常强烈的偏向性，特别是TCRAV1、-2、-5、-6、-7、-11、-12和-13。这些研究表明，HLA基因在决定Vα片段使用方面所起的作用比Vβ小。然而，Vα片段在CD4 +或CD8 +群体中的明显偏向性表明HLA基因在决定VαTCR库方面发挥了一定作用。此外，同卵双胞胎Vα库的惊人相似性表明非HLA基因在决定Vα库方面起主要作用。
