Minors held by majors: The H13 minor histocompatibility locus defined as a peptide MHC class I complex

The products of minor histocompatibility (H) loci are serious barriers to tissue transplantation even among major histocompatibility complex (MHC) identical individuals, frequently causing chronic graft rejection and graft versus host disease. Over 50 minor H loci map to mouse autosomal chromosomes but none are known at the molecular level. By expression cloning, we identified the H13 locus, a classical minor H locus first detected 30 years ago by the trait of graft rejection. The H13(a) allele is located on chromosome 2 and encodes a novel protein that yields the rare naturally processed nonapeptide SSVVGVWYL (SVL9) for presentation by the D-b MHC class I molecule. The SVL9 peptide binds Db MHC despite the absence of the consensus binding motif, and a conservative methyl group substitution (Valine 4 <--> Isoleucine) explains why reciprocal T cell responses are elicited in H13(a) and H13(b) congenic strains.