A CDNA CLONE ENCODING THE MOUSE QA-1(A) HISTOCOMPATIBILITY ANTIGEN AND PROPOSED STRUCTURE OF THE PUTATIVE PEPTIDE BINDING-SITE

We have isolated a cDNA clone which encodes the Qa-1a histocompatibili ty Ag from a library prepared from Con A-activated B10.BR mouse spleen cells. The clone encodes a protein of 322 amino acids with three pote ntial N-glycosylation sites. The coding sequence shows strongest simil arity with that of the T23d gene of DBA/2 mice which encodes the Qa-1b molecule. Molecular modeling of the putative peptide-combining site i ndicates most of the differences between Qa-1a and Qa-1b are located p eripheral to the binding cleft, with only two amino acid substitutions , at positions 9 and 24, which might affect peptide binding. Many feat ures of the Qa-1 binding cleft are also conserved in the rat RTBM.1 an d in human HLA-E molecules. This suggests that all of these molecules may associate with structurally similar peptides.