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.

Assembly and Function of the Major Histocompatibility Complex (MHC) I Peptide-loading Complex Are Conserved Across Higher Vertebrates

“…So far, peptide transport by the TAP complex has only been studied in a few species, namely human, mouse, rat, and chicken (5,(15)(16)(17)(18)(19). Here, we cloned, expressed, and analyzed the function of more than 20 heterodimeric TAP complexes across different taxa: six mammals (human, cow, pig, dog, mouse, rat: Homo sapiens, Bos taurus, Sus scrofa, Canis familiaris, Mus musculus, and Rattus norvegicus, respectively), and four birds (duck, quail, chicken, turkey: Anas platyrhynchos, Coturnix coturnix, Gallus gallus, and Meleagris gallopavo, respectively).…”