title: Asymptomatic deficiency in the peptide transporter associated to antigen processing (TAP).
abstract: Human HLA class I deficiency is a rare disease which, in most of the patients described to date, results from a defect in subunit 1 or 2 of the peptide transporter associated with antigen processing (TAP). The clinical features of TAP deficiency include a chronic inflammation of the respiratory tract and/or granulomatous skin lesions. In this report, we describe two adult siblings with an HLA class I deficiency. One individual had only spontaneously-healing skin granulomatous lesions, while the second did not display any of the symptoms associated with HLA class I deficiency and could be considered to be healthy. We show that the patients display a homozygous TAP2 mutation which blocks the maturation of HLA class I molecules. Cell surface expression of these molecules is strongly reduced, but three times higher than on cells from other previously described TAP-deficient individuals. This higher expression results, at least in part, from the presence of HLA-B7 molecules which are probably empty of peptide. The numbers of CD8+ alphabeta T cells are almost normal in these patients. The anti-EBV T-cell response of one patient is mediated by HLA-B7 restricted CD8+ alphabeta T lymphocytes recognizing the BMRF1 nuclear EBV antigen, demonstrating that CD8+ alphabeta T cells can participate in anti-viral responses. This study shows that TAP deficiency can remain totally asymptomatic for several decades, and suggests that in some cases, TAP-independent immune responses provide efficient protection from most of the common intracellular pathogens.
authors.affiliation: INSERM EP 99-08, Etablissement Français du Sang-Alsace, Strasbourg, France. henri.delasalle@efs-alsace.fr
authors.forename: H
authors.initials: H
authors.lastname: de la Salle
authors.forename: X
authors.initials: X
authors.lastname: Saulquin
authors.forename: I
authors.initials: I
authors.lastname: Mansour
authors.forename: S
authors.initials: S
authors.lastname: Klayme
authors.forename: D
authors.initials: D
authors.lastname: Fricker
authors.forename: J
authors.initials: J
authors.lastname: Zimmer
authors.forename: J-P
authors.initials: JP
authors.lastname: Cazenave
authors.forename: D
authors.initials: D
authors.lastname: Hanau
authors.forename: M
authors.initials: M
authors.lastname: Bonneville
authors.forename: E
authors.initials: E
authors.lastname: Houssaint
authors.forename: G
authors.initials: G
authors.lastname: Lefranc
authors.forename: R
authors.initials: R
authors.lastname: Naman
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000276:immunology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002461:Cell Line, Transformed; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D015793:HLA-B7 Antigen / Q000276:immunology; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000145:classification / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015793:HLA-B7 Antigen; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C071692:TAP2 protein, human