TAP POLYMORPHISM DOES NOT INFLUENCE TRANSPORT OF PEPTIDE VARIANTS IN MICE AND HUMANS

The major histocompatibility complex (MHC)-encoded transporter associa ted with antigen processing (TAP) delivers cytosolic peptides to the l umen of the endoplasmic reticulum (ER) for presentation by MHC class I molecules. For the rat, it has been demonstrated that TAP polymorphis m results in the selection of different sets of peptides, the nature o f the C terminus being of particular importance. Here, we investigated whether TAP polymorphism in mice and humans has functional consequenc es for transport of peptide sets variable at the C-terminal residues. Using cell lines of H-2(d), H-2(k), and H-2(dxk) haplotype and a panel of human lymphoblastoid cell lines expressing eight different TAP all eles, we detected species-specific transport patterns, but no signific ant influence of TAP polymorphism on peptide selection. In addition, p eptides with different core sequences were translocated to the same ex tent by different TAP. These results suggest that a major contribution of human TAP polymorphism to disease progression and autoimmunity is not very likely.