Sequence Polymorphism and Predicted Structural Variation in Chicken MHC YF Class I Molecules

Chicken MHC YF class I genes are intriguing polymorphic genes located on chicken chromosome 16 (GGA 16) near the classical MHC. Rather than being inherited in linkage with classical MHC genes, YF genes are linked with a set of olfactory receptor genes recently mapped to GGA 16. The function of YF genes is not known. The structure of YF1*7.1, determined in earlier work, revealed a narrow and hydrophobic binding groove quite distinct from the grooves of classical peptide-antigen-presenting MHC class I molecules and the ancient lipid-antigen-presenting molecules called CD1. YF1*7.1 shares some structural features with the mammalian MR1 molecules, which present bacterial metabolites for immune recognition. To begin to look further at YF function we have defined YF class I sequence variability displayed by the YF class I transcripts expressed from five well-defined MHC-Y haplotypes. We found that the number of transcripts varied from one to four among the five haplotypes. The sequences revealed considerable polymorphism. Most of the sequence variability was found within the region encoding the binding groove. Models for these isoforms, made using YF1*7.1 as the base structure, revealed variation in the shape, size and electrostatic potential of the YF binding groove suggesting that binding groove structural variability may be intrinsic to the function of the YF system. It may be that different YF isoforms bind different ligands and differentially affect the cell interactions in which YF molecules likely participate.