title: Positional cloning and molecular characterization of an immunodominant cytotoxic determinant of the mouse H3 minor histocompatibility complex.
abstract: Immune responses to minor histocompatibility antigens are poorly understood and present substantial barriers to successful solid tissue and bone marrow transplantation among MHC-matched individuals. We exploited a unique positional cloning approach relying on the potent negative selection capability of cytotoxic T cells to identify the H3a gene responsible for immunodominant H2-Db-restricted determinants of the classically defined mouse autosomal H3 complex. The allelic basis for reciprocal H3a antigens is two amino acid changes within a single nonamer H2-Db-binding peptide. The H3a gene, now called Zfp106, encodes a 1888-amino acid protein with three zinc fingers and a beta-transducin domain consistent with DNA/protein binding. A region of ZFP106 is identical to a 600-amino acid sequence implicated in the insulin receptor signaling pathway.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Zuberi
authors.forename: G J
authors.initials: GJ
authors.lastname: Christianson
authors.forename: L M
authors.initials: LM
authors.lastname: Mendoza
authors.forename: N
authors.initials: N
authors.lastname: Shastri
authors.forename: D C
authors.initials: DC
authors.lastname: Roopenian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002154:Calpain / Q000235:genetics; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics; D016056:Immunodominant Epitopes / Q000235:genetics*; D019656:Loss of Heterozygosity; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology*; D008912:Minor Histocompatibility Loci / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D010446:Peptide Fragments / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D016056:Immunodominant Epitopes; D015778:Minor Histocompatibility Antigens; D009124:Muscle Proteins; D010446:Peptide Fragments; C116200:Zfp106 protein, mouse; D002154:Calpain; C491373:Capn3 protein, mouse