αβ T cell receptor (TCR) V(D)J genes code for billions of TCR combinations. However, only some appear on peripheral T cells in any individual because, to mature, thymocytes must react with low affinity but not high affinity with thymus expressed major histocompatibility (MHC)/peptides. MHC proteins are very polymorphic. Different alleles bind different peptides. Therefore, any individual might express many different MHC alleles to ensure that some peptides from an invader are bound to MHC and activate T cells. However, most individuals express limited numbers of MHC alleles. To explore this, we compared the TCR repertoires of naïve CD4 T cells in mice expressing one or two MHC alleles. Unexpectedly, the TCRs in heterozygotes were less diverse that those in the sum of their MHC homozygous relatives. Our results suggest that thymus negative selection cancels out the advantages of increased thymic positive selection in the MHC heterozygotes.

中文翻译：

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MHC 杂合性限制了 CD4 T 细胞中 T 细胞受体的变异性


αβ T 细胞受体 （TCR） V（D）J 基因编码数十亿种 TCR 组合。然而，只有一些出现在任何个体的外周 T 细胞上，因为要成熟，胸腺细胞必须以低亲和力而不是高亲和力与胸腺表达的主要组织相容性 （MHC）/肽反应。MHC 蛋白具有很强的多态性。不同的等位基因结合不同的肽。因此，任何个体都可能表达许多不同的 MHC 等位基因，以确保来自入侵者的一些肽与 MHC 结合并激活 T 细胞。然而，大多数个体表达有限数量的 MHC 等位基因。为了探索这一点，我们比较了表达一个或两个 MHC 等位基因的小鼠中幼稚 CD4 T 细胞的 TCR 库。出乎意料的是，杂合子中的 TCR 比其 MHC 纯合亲属之和的 TCR 的多样性要小。我们的结果表明，胸腺阴性选择抵消了 MHC 杂合子中胸腺阳性选择增加的优势。