title: Human peptide transporter deficiency: importance of HLA-B in the presentation of TAP-independent EBV antigens.
abstract: Two siblings with a peptide TAP deficiency were recently described. Despite poor cell surface expression of HLA class I molecules, these patients were not unusually susceptible to viral infections. The majority of the cell surface-expressed class I molecules were HLA-B products as assessed by cytofluorometry and biochemical analysis. Analysis of two peptides eluted from the class I molecules expressed by TAP-deficient EBV B lymphoblastoid cell lines indicated that both were derived from cytosolic proteins and presented by HLA-B molecules. Peripheral alphabeta CD8+ T cells were present and their TCR repertoire was polyclonal. Most of the alphabeta CD8+ T cell clones studied (21 of 22) were nonreactive against cells expressing normal levels of the same HLA alleles as those of the TAP-deficient patients. However, it was possible to isolate one cytotoxic CD8+ alphabeta T cell clone recognizing the EBV protein LMP2 presented by HLA-B molecules on TAP-deficient cells. These observations suggest that in the TAP-deficient patients, CD8+ alphabeta T cells could mature and be recruited in immune responses to mediate HLA class I-restricted cytotoxic defense against viral infections. They also strengthen the physiologic importance of a TAP-independent processing pathway of the LMP2 protein, which was previously shown to contain several other TAP-independent epitopes.
authors.affiliation: Histocompatibility Laboratory, Contract for Young Research Unit INSERM 94-03 and INSERM Unit 311, Blood Transfusion Establishment, Strasbourg, France.
authors.forename: H
authors.initials: H
authors.lastname: de la Salle
authors.forename: E
authors.initials: E
authors.lastname: Houssaint
authors.forename: M A
authors.initials: MA
authors.lastname: Peyrat
authors.forename: D
authors.initials: D
authors.lastname: Arnold
authors.forename: J
authors.initials: J
authors.lastname: Salamero
authors.forename: D
authors.initials: D
authors.lastname: Pinczon
authors.forename: S
authors.initials: S
authors.lastname: Stevanovic
authors.forename: H
authors.initials: H
authors.lastname: Bausinger
authors.forename: D
authors.initials: D
authors.lastname: Fricker
authors.forename: E
authors.initials: E
authors.lastname: Gomard
authors.forename: W
authors.initials: W
authors.lastname: Biddison
authors.forename: P
authors.initials: P
authors.lastname: Lehner
authors.forename: F
authors.initials: F
authors.lastname: UytdeHaag
authors.forename: M
authors.initials: M
authors.lastname: Sasportes
authors.forename: L
authors.initials: L
authors.lastname: Donato
authors.forename: H G
authors.initials: HG
authors.lastname: Rammensee
authors.forename: J P
authors.initials: JP
authors.lastname: Cazenave
authors.forename: D
authors.initials: D
authors.lastname: Hanau
authors.forename: M M
authors.initials: MM
authors.lastname: Tongio
authors.forename: M
authors.initials: M
authors.lastname: Bonneville
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015235:HLA-B Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; D015235:HLA-B Antigens; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C071692:TAP2 protein, human