title: Expression of HLA class I antigens in transporter associated with antigen processing (TAP)-deficient mutant cell lines.
abstract: Cells lacking expression of the transporter associated with antigen processing (TAP) are deficient in surface HLA class I, yet express reduced levels of HLA-A2 antigen through TAP-independent processing pathways. We have analysed the expression of HLA-A, -B and -C antigens on the 721.174 and T2 TAP-deficient mutant cell lines using a panel of monoclonal antibodies specific for the HLA antigens encoded by the genotype of these cells. Our study has shown the constitutive expression of HLA-Cw1 molecules on the cell surface of both T2 and 721.174 cells and has confirmed that HLA-A2 and HLA-B51 are expressed at low levels. Transfection of 721.174 cells with cDNAs encoding TAP1 and TAP2 proteins did not fully restore HLA class I antigen expression on these cells, which appeared to be mainly due to a deficiency in expression of the HLA-B51-associated Bw4 epitope. This suggests that additional antigen-processing genes may be required for optimal generation of HLA-B-binding peptides. Our results indicate that TAP-independent pathways of antigen-processing provide peptides for functional expression of all three classical HLA class I molecules.
authors.affiliation: Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, UK. nyoung@cmgm.stanford.edu
authors.forename: N T
authors.initials: NT
authors.lastname: Young
authors.forename: A
authors.initials: A
authors.lastname: Mulder
authors.forename: V
authors.initials: V
authors.lastname: Cerundolo
authors.forename: F H
authors.initials: FH
authors.lastname: Claas
authors.forename: K I
authors.initials: KI
authors.lastname: Welsh
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D005434:Flow Cytometry; D005838:Genotype; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex; D051379:Mice
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D006680:HLA Antigens; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; C071692:TAP2 protein, human