Minors Held by Majors: The H13Minor Histocompatibility Locus Defined as a Peptide/MHC Class I Complex

AbstractThe 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 H13a 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 D b 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 H13a and H13 b congenic strains