The dominantly expressed class I molecule of the chicken MHC is explained by coevolution with the polymorphic peptide transporter (TAP) genes

Abstract

In most mammals, the MHC class I molecules are polymorphic and determine the specificity of peptide presentation, whereas the transporter associated with antigen presentation (TAP) heterodimers are functionally monomorphic. In chickens, there are two classical class I genes but only one is expressed at a high level, which can result in strong MHC associations with resistance to particular infectious pathogens. However, the basis for having a single dominantly expressed class I molecule has been unclear. Here we report TAP1 and TAP2 sequences from 16 chicken lines, and show that both genes have high allelic polymorphism and moderate sequence diversity, with variation in positions expected for peptide binding. We analyze peptide translocation in two MHC haplotypes, showing that chicken TAPs specify translocation at three peptide positions, matching the peptide motif of the single dominantly expressed class I molecule. These results show that coevolution between class I and TAP genes can explain the presence of a single dominantly expressed class I molecule in common chicken MHC haplotypes. Moreover, such coevolution in the primordial MHC may have been responsible for the appearance of the antigen presentation pathways at the birth of the adaptive immune system. avian | evolution | bird

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

“…The ancestral abcb9 gene is largely monomorphic, unlike the polymorphic tap1 and tap2 genes found in many jawed vertebrates. For example, the derived tap1 gene was found to be highly polymorphic in some species, such as Xenopus (43) and chicken (26). Similarly, polymorphic alleles for tap2 have also been found in several species (Fig.…”

“…Chickens represent another interesting exception, because antigen processing genes from the first stage of the MHC pathway, the inducible proteasome subunits proteasome-β 8-10 (psmb8-10), are altogether missing (25). However, this lack of inducible proteasome subunits in chickens does not seem to have reduced the capacity for polymorphic antigen transport genes, encoding the TAP subunits, to coevolve distinctive peptide specificities with coinherited MHCI alleles (26).…”

Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer

“…Cells were detached by using PBS with 2 mM EDTA, cell pellets were lysed on ice for 30 min in a lysis buffer [100 mM TrisCl, 150 mM NaCl, 1 mM MgCl 2 , 0.5 mM 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride, and 1% digitonin], and the lysates were clarified by centrifugation to give 10 8 cells per mL, as described (35). The total protein in lysates was measured by using Bradford Reagent (Sigma) following the manufacturer's instructions.…”

“…The total protein in lysates was measured by using Bradford Reagent (Sigma) following the manufacturer's instructions. Electrophoresis and blotting was performed as described (35) with the primary antibody, a tissue culture supernatant containing mAb TD50, and incubated overnight at 4°C. To ensure equal loading of all samples gels were stained with Commassie Brilliant Blue posttransfer and membranes were stripped (Restore Stripping Buffer; Thermo Scientific) and blotted with a primary actin antibody (clone AC-15; Sigma) according to the manufacturer's instructions.…”

Extensive Allelic Diversity of MHC Class I in Wild Mallard Ducks

“…This has led to the hypothesis that linkage of the MHC class I gene to TAP genes constrains expression of additional MHC class I genes (13). In the chicken, the transporters for Ag processing (TAPs) can transport best the peptides that will fit the allele at the adjacent BF2 locus (21). The genes at BF1 show limited polymorphism and are expressed at one-tenth the level of BF2 (22).…”