Expressed Peromyscus maniculatus (Pema) MHC class I genes: evolutionary implications and the identification of a gene encoding a Qa1-like antigen.

To gain insight into the evolution of rodent major histocompatibility complex (MHC) class I genes and identify important (conserved) nonclassical class I (class I b) gene products and residues in these proteins, six Peromyscus maniculatus MHC (Pema) class I cDNA clones were isolated and sequenced. Five Pema class I cDNAs appeared most similar to mouse and rat classical class I (class I a) genes. One exhibited highest similarity to an H2 class I b gene, H2-T23 (encoding the Qa1 antigen). Phylogenetic trees constructed with Pema, RT1, and H2 class I sequences suggested that the lineages of some rodent class I b genes (e. g., T23 and T24) originated prior to Mus and Peromyscus speciation [>50 million years (My) ago]. Sequences of four Qa1-like proteins from three species permitted the identification of ten Qa1-specific amino acids. On the basis of molecular modeling, three residues showed the potential to interact with T-cell receptors and three residues (all corresponding to polymorphic positions among H2 class I a proteins) were predicted to influence antigen binding. The recognition of mouse Qa1 proteins by a subset of T-cells in influenced by a locus, Qdm, which encodes the H2-D leader peptide. One of the Pema class I cDNA clones classified as H2-K, D/L-like (class I a) is predicted to encode an identical peptide, implying that an antigen binding protein (Qa1) and the antigen to which it binds (the product of Qdm) has been conserved for over 50 My.