Sequence of a cDNA coding for a rat class II A alpha chain: extensive DNA and protein sequence identity to H-2 A...

The rat major histocompatibility complex (RT1-B region) codes for two sets of class II molecules (Ia antigens) referred to as A and E. Each class II molecule is composed of two glycoprotein chains called the A alpha and A beta or E alpha and E beta. Two cDNA clones encoding rat A alpha chains were identified from cDNA derived from rat spleen mRNA using a combination of mRNA selection and colony hybridization techniques. The complete nucleotide sequence of the cDNA insert of one of these cDNA clones, pRIa.2, was determined. This sequence codes for the carboxy-terminal 129 amino acids of the rat A alpha chain and 293 nucleotides of 3' untranslated sequence. The rat A alpha chain was shown to be highly homologous in terms of both protein and DNA sequence identities to HLA-DC1 alpha and H-2 A alpha chains. Comparison between the coding regions of the cDNA insert of pRIa.2 and the corresponding region of a cDNA insert encoding an HLA-DC1 alpha chain showed sequence identities of 85% and 81% at the protein and DNA levels, respectively. Comparison between pRIa.2 and cDNA encoding an H-2 A alpha chain sequence showed identities of 91% for both protein and DNA. Results are discussed which strongly suggest that the class II A and E primordial genes arose by gene duplication prior to the evolutionary divergence of the mammals.