Distinctive polymorphism of chicken B-FI (major histocompatibility complex class I) molecules

The major histocompatibility complex (MHC) in chickens influences disease resistance, but the mechanism is not understood. In Leghorn lines, the MHC contains 2 closely-linked class I loci, B-FI and B-FIV. Previously, we determined nucleotide sequences of well-expressed class I (B-F) genes from unique MHC haplotypes of broiler chicken lines. More recently, we identified 7 new B-F alpha1alpha2-coding sequences from less well-expressed loci by amplification of genomic DNA from unique broiler haplotypes. Phylogenetic analysis of chicken MHC class I alpha1alpha2-coding sequences resolved 2 clusters (Groups A and B), which appear to correspond to B-FIV and B-FI loci, respectively. Compared with B-FIV locus, B-FI alleles were less polymorphic overall, but nevertheless demonstrated evidence of diversifying selection. The most striking feature of B-FI alleles is a conserved, locus-specific motif in the alpha helix of the alpha1 domain, a region that is highly variable in B-FIV alleles. This distinctive pattern of allelic polymorphism resembles that of the HLA-C class I locus in the human MHC (HLA). The conservation of the alpha helix of the alpha1 domain relates to HLA-C interaction with members of the killer immunoglobulin-like receptors on natural killer (NK) cells that are specific for recognition of HLA-C molecules and function to regulate activation of NK cells. Whereas HLA-C molecules may be dominant ligands for NK cell regulation, HLA-A and -B molecules are more important in presenting antigen to cytotoxic T lymphocytes. We hypothesize that chicken B-FI molecules may be specialized to serve similar functions as HLA-C molecules.