Bonobos Maintain Immune System Diversity with Three Functional Types of MHC-B

Abstract

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 <i>HLA class I</i>, their study gives unique perspectives on the human condition. We defined polymorphism of <i>Papa-B</i>, the bonobo ortholog of <i>HLA-B</i>, for six wild bonobo populations. Sequences for <i>Papa-B</i> exon 2 and 3 were determined from the genomic DNA in 255 fecal samples, minimally representing 110 individuals. Twenty-two <i>Papa-B</i> 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 α₁ 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 <i>Papa-B</i> in Malebo is greater than in the other populations and is also greater than expected for random combinations of three <i>Papa-B</i> Overall, <i>Papa-B</i> has substantially less diversity than <i>Patr-B</i> in chimpanzee subspecies and <i>HLA-B</i> in indigenous human populations, consistent with bonobo having experienced narrower population bottlenecks.