THE MOLECULAR AND FUNCTIONAL-CHARACTERIZATION OF A DOMINANT MINOR H-ANTIGEN, H60

Minor histocompatibility (EF) Ags elicit T cell responses and thereby cause chronic graft rejection and graft-vs-host disease among MHC iden tical individuals, Although numerous independent H loci exist in mice of a given MHC haplotype, certain H Ags dominate the immune response a nd are thus of considerable conceptual and therapeutic importance. To identify these H Ags and their genes, lacZ-inducible CD8(+) T cell hyb rids were generated by immunizing C57BL/6 (B6) mice with MHC identical BALB.B spleen cells. The cDNA clones encoding the precursor for the a ntigenic peptide/K-b MHC class I complex were isolated by expression c loning using the BCZ39.84 T cell as a probe. The cDNAs defined a new H locus (termed H60), located on mouse chromosome 10, and encoded a nov el protein that contains the naturally processed octapeptide LTFNYRNL (LYL8) presented by the K-b MHC molecule. Southern blot analysis revea led that the H60 locus was polymorphic among the BALE and the B6 strai ns. However, none of the H60 transcripts expressed in the donor BALE s pleen were detected in the host B6 strain. The expression and immunoge nicity of the LYL8/K-b complex in BALB.B and CXB recombinant inbred st rains strongly suggested that the H60 locus may account for one of the previously described antigenic activity among these strains. The resu lts establish the source of an immunodominant autosomal minor II Ag th at, by its differential transcription in the donor vs the host strains , provides a novel peptide/MHC target for host CD8(+) T cells.