The properties of the single chicken MHC classical class II ? chain (B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules

In mammals, there are MHC class II molecules with distinctive sequence features, such as the classical isotypes DR, DQ and DP. These particular isotypes have not been reported in non-mammalian vertebrates. We have isolated the class II (B-L) α chain from outbred chickens as the basis for the cloning and sequencing of the cDNA. We found only one class II α chain transcript, which bears the major features of a classical class II α sequence, including the critical peptide-binding residues. The chicken sequence is more similar to human DR than to the DQ, DP, DO or DM isotypes, most significantly in the peptide-binding α^sub 1^ domain. The cDNA and genomic DNA sequences from chickens of diverse origins show few alleles, which differ in only four nucleotides and one amino acid. In contrast, significant restriction fragment length polymorphism is detected by Southern blot analysis of genomic DNA, suggesting considerable diversity around the gene. Analysis of a large back-cross family indicates that the class II α chain locus (B-LA) is located roughly 5.6 cM from the MHC locus, which encodes the classical class II β chains. Thus the chicken class II α chain gene is like the mammalian DR and E isotypes in three properties: the presence of the critical peptide-binding residues, the low level of polymorphism and sequence diversity, and the recombinational separation from the class II β chain genes. These results indicate that the sequence features of this lineage are both functionally important and at least 300 million years old.[PUBLICATION ABSTRACT]