Zemmour J, Koller B H, Ennis P D, Geraghty D E, Lawlor D A, Orr H T, Parham P
Department of Cell Biology, Stanford University, CA 94305.
J Immunol. 1990 May 1;144(9):3619-29.
The MHC contains many class I genes other than those known to present peptides to T lymphocytes. These additional class I genes vary between species and their functions are unknown. Genes involved in Ag presentation, HLA-A,B,C in humans, are highly diverse whereas other class I genes are of much more limited diversity. We have studied alleles of a gene, HLA-AR, that is closely linked and structurally related to HLA-A; properties consistent with these two loci having been formed by a gene duplication. Compared to HLA-A the diversity in HLA-AR is much less, and does not focus on residues of a putative Ag recognition site. However, the structure of HLA-AR alleles closely resembles those encoding Ag-presenting molecules, although the presence of one or two deleterious mutations prevents these alleles being active in Ag presentation. These results suggest HLA-AR derives from an Ag-presenting locus that became inactivated, possibly as a result of positive natural selection due to changing demands on T cell immunity. Thus absence of diversity may sometimes correlate with loss rather than preservation of function in class I MHC genes.
主要组织相容性复合体（MHC）包含许多I类基因，除了那些已知可向T淋巴细胞呈递肽段的基因。这些额外的I类基因在不同物种间存在差异，其功能尚不清楚。参与抗原呈递的基因，如人类的HLA - A、B、C，具有高度多样性，而其他I类基因的多样性则较为有限。我们研究了一个与HLA - A紧密连锁且结构相关的基因HLA - AR的等位基因；其特性与这两个基因座由基因复制形成一致。与HLA - A相比，HLA - AR的多样性要少得多，并且不集中在假定的抗原识别位点的残基上。然而，HLA - AR等位基因的结构与编码抗原呈递分子的结构非常相似，尽管存在一两个有害突变，阻止了这些等位基因在抗原呈递中发挥作用。这些结果表明，HLA - AR源自一个失活的抗原呈递基因座，可能是由于对T细胞免疫的需求变化导致正向自然选择的结果。因此，I类MHC基因多样性的缺失有时可能与功能丧失而非保留相关。
