Adams E J, Cooper S, Parham P
Department of Integrative Biology, University of California, Berkeley, CA 94720, USA.
J Immunol. 2001 Oct 1;167(7):3858-69. doi: 10.4049/jimmunol.167.7.3858.
All expressed human MHC class I genes (HLA-A, -B, -C, -E, -F, and -G) have functional orthologues in the MHC of the common chimpanzee (Pan troglodytes). In contrast, a nonclassical MHC class I gene discovered in the chimpanzee is not present in humans or the other African ape species. In exons and more so in introns, this Patr-AL gene is similar to the expressed A locus in the orangutan, Popy-A, suggesting they are orthologous. Patr-AL/Popy-A last shared a common ancestor with the classical MHC-A locus >20 million years ago. Population analysis revealed little Patr-AL polymorphism: just three allotypes differing only at residues 52 and 91. Patr-AL is expressed in PBMC and B cell lines, but at low level compared with classical MHC class I. The Patr-AL polypeptide is unusually basic, but its glycosylation, association with beta(2)-microglobulin, and antigenicity at the cell surface are like other MHC class I. No Patr-AL-mediated inhibition of polyclonal chimpanzee NK cells was detected. The Patr-AL gene is present in 50% of chimpanzee MHC haplotypes, correlating with presence of a 9.8-kb band in Southern blots. The flanking regions of Patr-AL contain repetitive/retroviral elements not flanking other class I genes. In sequenced HLA class I haplotypes, a similar element is present in the A2901 haplotype but not the A0201 or A0301 haplotypes. This element, 6 kb downstream of A2901, appears to be the relic of a human gene related to Patr-AL. Patr-AL has characteristics of a class I molecule of innate immunity with potential to provide common chimpanzees with responses unavailable to humans.
所有已表达的人类主要组织相容性复合体（MHC）I类基因（HLA - A、- B、- C、- E、- F和 - G）在普通黑猩猩（Pan troglodytes）的MHC中都有功能直系同源基因。相比之下，在黑猩猩中发现的一个非经典MHC I类基因在人类或其他非洲猿类物种中不存在。在外显子中，尤其是在内含子中，这个Patr - AL基因与猩猩中已表达的A位点Popy - A相似，表明它们是直系同源的。Patr - AL/Popy - A在2000多万年前与经典的MHC - A位点最后共享一个共同祖先。群体分析显示Patr - AL多态性很少：只有三种同种异型，仅在第52和91位残基处不同。Patr - AL在PBMC和B细胞系中表达，但与经典MHC I类相比水平较低。Patr - AL多肽异常碱性，但其糖基化、与β2 - 微球蛋白的结合以及在细胞表面的抗原性与其他MHC I类相似。未检测到Patr - AL介导的对黑猩猩多克隆自然杀伤细胞的抑制作用。Patr - AL基因存在于50%的黑猩猩MHC单倍型中，与Southern印迹中9.8 kb条带的存在相关。Patr - AL的侧翼区域包含其他I类基因侧翼不存在的重复/逆转录病毒元件。在已测序的HLA I类单倍型中，一个类似的元件存在于A2901单倍型中，但不存在于A0201或A0301单倍型中。这个元件位于A2901下游6 kb处，似乎是与Patr - AL相关的人类基因的遗迹。Patr - AL具有先天免疫I类分子的特征，有可能为普通黑猩猩提供人类无法获得的反应。
