title: Structural analysis of H-2Kf and H-2Kfm1 by using H-2K locus-specific sequences.
abstract: The H-2Kf allele and the spontaneous mutant Kfm1 have been cloned using locus-specific sequences. The mutation consists of a cluster of four nucleotide changes, resulting in amino acid substitutions at positions 95 (Leu----Ile) and 97 (Val----Arg). This finding has structural, genetic, and technical implications. The amino acid substitutions are located on the beta-strands of the antigen recognition site. Their influence on the allogeneic properties of the Kf glycoprotein is consistent with the hypothesis that alloreactivity results from alterations in the spectrum of peptides presented to T cells. These substitutions would not, however, be predicted to be directly accessible for binding to antibodies. Nonetheless, the fm1 mutant binds anti Kf alloantisera and mAb much less strongly than the parent molecule, suggesting some indirect effect of these residues on serologic phenotype. The mutant is also interesting genetically because the sequence of the mutated region is identical to the sequence of the Df gene. This implies that there is a gene conversion-like mutational mechanism operating in the H-2f haplotype. Finally, the strategy used to obtain these K-locus cDNA should prove generally useful for isolating other MHC alleles.
authors.affiliation: Department of Immunology, Mayo Graduate School, Rochester, MN 55905.
authors.forename: R M
authors.initials: RM
authors.lastname: Horton
authors.forename: W H
authors.initials: WH
authors.lastname: Hildebrand
authors.forename: J M
authors.initials: JM
authors.lastname: Martinko
authors.forename: L R
authors.initials: LR
authors.lastname: Pease
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005091:Exons; D006183:H-2 Antigens / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D006183:H-2 Antigens; D009841:Oligonucleotides; D012333:RNA, Messenger