title: Human CD8+ T cell responses to EBV EBNA1: HLA class I presentation of the (Gly-Ala)-containing protein requires exogenous processing.
abstract: Epstein-Barr virus (EBV)-induced cytotoxic T lymphocyte (CTL) responses have been detected against many EBV antigens but not the nuclear antigen EBNA1; this has been attributed to the presence of a glycine-alanine repeat (GAr) domain in the protein. Here we describe the isolation of human CD8+ CTL clones recognizing EBNA1-specific peptides in the context of HLA-B35.01 and HLA-A2.03. Using these clones, we show that full-length EBNA1 is not presented when expressed endogenously in target cells, whereas the GAr-deleted form is presented efficiently. However, when supplied as an exogenous antigen, the full-length protein can be presented on HLA class I molecules by a TAP-independent pathway; this may explain how EBNA1-specific CTLs are primed in vivo.
authors.affiliation: CRC Institute for Cancer Studies, University of Birmingham, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Blake
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: I
authors.initials: I
authors.lastname: Redchenko
authors.forename: W
authors.initials: W
authors.lastname: Thomas
authors.forename: N
authors.initials: N
authors.lastname: Steven
authors.forename: A
authors.initials: A
authors.lastname: Leese
authors.forename: P
authors.initials: P
authors.lastname: Steigerwald-Mullen
authors.forename: M G
authors.initials: MG
authors.lastname: Kurilla
authors.forename: L
authors.initials: L
authors.lastname: Frappier
authors.forename: A
authors.initials: A
authors.lastname: Rickinson
mesh_terms: D000409:Alanine / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D002999:Clone Cells; D018900:Dinucleotide Repeats / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005998:Glycine / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D015234:HLA-A Antigens; D000409:Alanine; D005998:Glycine