Coevolution of MHC genes (LMP/TAP/class Ia, NKT‐class Ib, NKp30‐B7H6): lessons from cold‐blooded vertebrates

Abstract

Summary Comparative immunology provides the long view of what is conserved across all vertebrate taxa versus what is specific to particular organisms or group of organisms. Regarding the major histocompatibility complex (MHC) and coevolution, three striking cases have been revealed in cold-blooded vertebrates: lineages of class Ia antigen-processing and -presenting genes, evolutionary conservation of NKT-class Ib recognition, and the ancient emergence of the natural cytotoxicity receptor NKp30 and its ligand B7H6. While coevolution of transporter associated with antigen processing (TAP) and class Ia has been documented in endothermic birds and two mammals, lineages of LMP7 are restricted to ectotherms. The unambiguous discovery of natural killer T (NKT) cells in Xenopus demonstrated that NKT cells are not restricted to mammals and are likely to have emerged at the same time in evolution as classical α/β and γ/δ T cells. NK cell receptors evolve at a rapid rate, and orthologues are nearly impossible to identify in different vertebrate classes. By contrast, we have detected NKp30 in all gnathostomes, except in species where it was lost. The recently discovered ligand of NKp30, B7H6, shows strong signs of coevolution with NKp30 throughout evolution, i.e. coincident loss or expansion of both genes in some species. NKp30 also offers an attractive IgSF candidate for the invasion of the RAG transposon, which is believed to have initiated T-cell receptor/immunoglobulin adaptive immunity. Besides reviewing these intriguing features of MHC evolution and coevolution, we offer suggestions for future studies and propose a model for the primordial or proto MHC.

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

“…Accordingly, compared with nonmammalian vertebrates, mammalian antigen processing genes are much less polymorphic, and mammalian MHC pathway diversity remains instead focused primarily in the MHCI genes. These findings are consistent with an immune strategy favoring the cleavage and transport of a more "generic" peptide repertoire, with greater emphasis on the downstream peptide binding specificities using a collection of diverse MHCI molecules (21)(22)(23).…”

“…Taken together, these findings represent the most extensive diversity yet identified within the antigen processing genes of any species. Evidence of allelic variation for some antigen processing genes had been lacking (23), despite examination of numerous species across major vertebrate lineages. Therefore, our work addresses previously unrecognized gaps in our understanding of the evolution of vertebrate MHC regions, including identification of deeply divergent lineages for additional classes of proteasome and TAP subunits.…”

“…Because of stable haplotypes, coinherited genes may have accumulated their genetic diversity primarily because of this shared genomic location, maintaining deep lineages that parallel the divergent psmb8f and mhc1uga genes. Conversely, these genes may have developed their tight linkage primarily because of their cooperative and exclusive roles in enhancing shared MHC pathway function (23,55). Maintaining a stable haplotypic structure would then help avoid sequence exchange events, such as recombination, that would interfere with coinherited gene function (56,57) and thus, maintain efficiency of the MHC pathway.…”

Evolution of the immune system influences speciation rates in teleost fishes

“…3a, Supplementary Table 13 and Supplementary Note). This model is characterized by a phylogenetic half-life of 23 million years, a stationary variance of 0.38 squared log copy numbers and an optimum of 6.8 MHC I copies for basal branches of the phylogeny, which is in concordance with the hypothesized MHC I repertoire of early gnathostomes 43 . In contrast, substantially higher optimal MHC I copy numbers of up to 58 copies were inferred within gadiform and percomorph fishes.…”

A cold-blooded view of adaptive immunity

“…Again, biochemical work was done long ago in amphibians, in which MHC class I proteins were isolated using cross-reactive xenoantisera, alloantisera and monoclonal antibodies 119,125 . Now, it is time to step up with studies examining associations with peptides and the importance of linkage 24 .…”