title: Characterization and allelic variation of the transporters associated with antigen processing (TAP) genes in the domestic dog (Canis lupus familiaris).
abstract: The function of the transporters associated with antigen processing (TAP) complex is to shuttle antigenic peptides from the cytosol to the endoplasmic reticulum to load MHC class I molecules for CD8(+) T-cell immunosurveillance. Here we report the promoter and coding regions of the canine TAP1 and TAP2 genes, which encode the homologous subunits forming the TAP heterodimer. By sampling genetically divergent breeds, polymorphisms in both genes were identified, although there were few amino acid differences between alleles. Splice variants were also found. When aligned to TAP genes of other species, functional regions appeared conserved, and upon phylogenetic analysis, canine sequences segregated appropriately with their orthologs. Transfer of the canine TAP2 gene into a murine TAP2-defective cell line rescued surface MHC class I expression, confirming exporter function. This data should prove useful in investigating the association of specific TAP defects or alleles with immunity to intracellular pathogens and cancer in dogs.
authors.affiliation: Immunology Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Gojanovich
authors.forename: Peter
authors.initials: P
authors.lastname: Ross
authors.forename: Savannah G
authors.initials: SG
authors.lastname: Holmer
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Holmes
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hess
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D002460:Cell Line; D004285:Dogs; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D019596:Wolves / Q000235:genetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms
keywords: ABC; ATP-binding cassette; Ab; Alleles; CDS; CL; Canine; DLA; EST; GAS; GFP; HLA; IFN; IFN-stimulated response element; IFR; ISRE; Immunology; MED1; NBD; ORF; PBMC; PKR; RLM-RACE; RNA ligase-mediated rapid amplification of cDNA ends; SNP; STAT; SV; Splice variants; TAP; TMD; TSS; Transporter associated with antigen processing; UTR; antibody; code determining sequence; cytosolic loop; dog leukocyte antigen; expressed sequence tag; gamma activating sequence; green fluorescent protein; human leukocyte antigen; interferon; interferon regulatory factor; multiple start site element downstream1; nucleotide-binding domain; open reading frame; peripheral blood mononuclear cells; protein kinase R; signal transducers and activators of transcription; single nucleotide polymorphism; splice variant; transcription start site; transmembrane domain; transporter associated with antigen processing; untranslated region; β2-microglobulin; β2M
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