PEPTIDE-TRANSPORT IN HUMAN LYMPHOBLASTOID AND TUMOR-CELLS - EFFECT OFTRANSPORTER ASSOCIATED WITH ANTIGEN PRESENTATION (TAP) POLYMORPHISM

CD8(+) T-cells recognize antigenic peptides presented by major histoco mpatibility complex (MHC) class I molecules. These peptides bind to MH C class I molecules in the endoplasmic reticulum (ER) lumen. Antigenic peptides are translocated from the cytosol to the lumen of ER by tran sporter associated with antigen presentation (TAP) proteins. In this s tudy, it is shown that TAP1 polymorphism influences the peptide substr ate specificity in human B-lymphoblastoid and tumor cell lines. TAP1A and 1C alleles specifically enhance translocation of model peptides co ntaining basic C-terminal amino acid residue. However, TAP1B allele do es not show specificity for the peptide C-terminus. Human basophilic l eukemia (Ku812), and hepatocellular carcinoma (PLC/PRF/5) cells expres s TAP1 molecules and exhibit TAP-mediated allele-specific peptide upta ke after gamma-interferon (gamma-IFN) treatment. Ku812 cells express T AP1A and preferentially take up antigenic peptides with a basic C-term inus, however, PLC/PRF/5 cells with the TAP1B allele take up low but e quivalent levels of peptides regardless of basic, acidic, or hydrophob ic C-termini. Moreover, TAP1 polymorphisms have no influence on the pe ptide translocation in normal or tumor cell lines. In addition, Daudi, a beta(2)-microglobulin (beta(2)m) deficient human Burkitt lymphoma, cell line also showed TAP-dependent peptide uptake. Taken together, th ese results suggest that human TAP1 but not TAP2 polymorphisms influen ce the antigenic peptide transport and that this transport is independ ent of beta(2)m in this system. (C) 1998 Elsevier Science B.V. All rig hts reserved.