Complete structure of a rat RT1 E beta chain: extensive conservation of MHC class II beta chains

The rat major histocompatibility complex (RT1 complex) encodes two sets of class II molecules, A alpha A beta and E alpha E beta. A cDNA clone encoding a RT1 E beta chain was isolated from a cDNA library prepared from Wistar (RT1 mu) spleen poly(A) RNA by screening with DNA fragments encoding a RT1 A beta chain. The nucleotide sequence of this cDNA insert was determined and was shown to encode a complete RT1 E beta chain. The RT1 E beta chain was highly homologous in terms of sequence identities to H-2 E beta and HLA-DR beta chains. Comparisons of predicted protein sequences of RT1, H-2, and HLA E beta and A beta chains showed that class II beta-chains are highly conserved with 105 out of 278 residues identical in all six beta-chains. The divergences in terms of the number of silent and replacement nucleotide substitutions between class II E beta or A beta sequences showed that the number of replacement substitutions reached a plateau after 10 million yr. Replacement substitutions therefore may be under selective pressure during evolution. The accumulation of silent and replacement substitutions in RT1 and H-2 class II beta-chains was faster than that in HLA beta-chain sequences. Thus, it appears that class II beta chains may be evolving at different rates in different species.