Faculty Research 1990 - 1999

Title

Positional cloning and molecular characterization of an immunodominant cytotoxic determinant of the mouse H3 minor histocompatibility complex.

Document Type

Article

Publication Date

1998

Keywords

Amino-Acid-Sequence, Animal, Base-Sequence, Calpain: ge, Chromosome-Mapping, Cloning-Molecular, DNA-Binding-Proteins: ge, Immunodominant-Epitopes: ge, Loss-of-Heterozygosity, Mice, Mice-Inbred-C57BL, Minor-Histocompatibility-Antigens: ge, im, Minor-Histocompatibility-Loci: ge, Molecular-Sequence-Data, Peptide-Fragments: ge, Sequence-Homology-Amino-Acid, Sequence-Homology-Nucleic-Acid, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes-Cytotoxic: ph

JAX Source

Immunity 1998 Nov;9(5):687-98

Grant

RO1AI28802/AI/NIAID, AI24544/AI/NIAID, CA34196/CA/NCI

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.

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