Wroblewski Emily E, Guethlein Lisbeth A, Norman Paul J, Li Yingying, Shaw Christiana M, Han Alex S, Ndjango Jean-Bosco N, Ahuka-Mundeke Steve, Georgiev Alexander V, Peeters Martine, Hahn Beatrice H, Parham Peter
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
J Immunol. 2017 May 1;198(9):3480-3493. doi: 10.4049/jimmunol.1601955. Epub 2017 Mar 27.
Fast-evolving MHC class I polymorphism serves to diversify NK cell and CD8 T cell responses in individuals, families, and populations. Because only chimpanzee and bonobo have strict orthologs of all , their study gives unique perspectives on the human condition. We defined polymorphism of , the bonobo ortholog of , for six wild bonobo populations. Sequences for exon 2 and 3 were determined from the genomic DNA in 255 fecal samples, minimally representing 110 individuals. Twenty-two alleles were defined, each encoding a different Papa-B protein. No Papa-B is identical to any chimpanzee Patr-B, human HLA-B, or gorilla Gogo-B. Phylogenetic analysis identified a clade of MHC-B, defined by residues 45-74 of the α domain, which is broadly conserved among bonobo, chimpanzee, and gorilla. Bonobo populations have 3-14 Papa-B allotypes. Three Papa-B are in all populations, and they are each of a different functional type: allotypes having the Bw4 epitope recognized by killer cell Ig-like receptors of NK cells, allotypes having the C1 epitope also recognized by killer cell Ig-like receptors, and allotypes having neither epitope. For population Malebo, these three Papa-B are the only Papa-B allotypes. Although small in number, their sequence divergence is such that the nucleotide diversity (mean proportional distance) of in Malebo is greater than in the other populations and is also greater than expected for random combinations of three Overall, has substantially less diversity than in chimpanzee subspecies and in indigenous human populations, consistent with bonobo having experienced narrower population bottlenecks.
快速进化的MHC I类多态性有助于个体、家族和群体中自然杀伤细胞(NK细胞)和CD8 T细胞反应的多样化。由于只有黑猩猩和倭黑猩猩拥有所有基因的严格直系同源物,对它们的研究为人类状况提供了独特的视角。我们定义了六个野生倭黑猩猩群体中与人类HLA - B基因直系同源的Papa - B基因的多态性。从255份粪便样本中的基因组DNA确定了Papa - B基因外显子2和3的序列,这些样本最少代表110个个体。定义了22个Papa - B等位基因,每个等位基因编码一种不同的Papa - B蛋白。没有一个Papa - B与任何黑猩猩的Patr - B、人类的HLA - B或大猩猩的Gogo - B相同。系统发育分析确定了一个由α结构域的45 - 74位氨基酸残基定义的MHC - B进化枝,在倭黑猩猩、黑猩猩和大猩猩中广泛保守。倭黑猩猩群体有3 - 14种Papa - B同种异型。有三种Papa - B存在于所有群体中,并且它们各自属于不同的功能类型:具有被NK细胞的杀伤细胞免疫球蛋白样受体识别的Bw4表位的同种异型、也被杀伤细胞免疫球蛋白样受体识别的C1表位的同种异型,以及没有这两种表位的同种异型。对于Malebo群体,这三种Papa - B是仅有的Papa - B同种异型。尽管数量较少,但它们的序列差异使得Malebo群体中Papa - B的核苷酸多样性(平均比例距离)大于其他群体,并且也大于三个随机组合的预期值。总体而言,Papa - B的多样性比黑猩猩亚种中的HLA - B以及土著人类群体中的HLA - B要少得多,这与倭黑猩猩经历了更窄的种群瓶颈一致。