title: Autoreactive cytotoxic T lymphocytes in human immunodeficiency virus type 1-infected subjects.
abstract: A subtractive analysis of peptides eluted from major histocompatibility complex (MHC) class I human histocompatibility leukocyte antigen (HLA)-A2.1 molecules purified from either human immunodeficiency virus type-1 (HIV-1)-infected or uninfected cells was performed using micro high-performance liquid chromatography and mass spectrometry. Three peptides unique to infected cells were identified and found to derive from a single protein, human vinculin, a structural protein not known to be involved in viral pathogenesis. Molecular and cytofluorometric analyses revealed vinculin mRNA and vinculin protein overexpression in B and T lymphocytes from HIV-1-infected individuals. Vinculin peptide-specific CTL activity was readily elicited from peripheral blood lymphocytes of the majority of HLA-A2.1+, HIV+ patients tested. Our observations suggest that atypical vinculin expression and MHC class I-mediated presentation of vinculin-derived peptides accompany HIV infection of lymphoid cells in vivo, with a resultant induction of antivinculin CTL in a significant portion of HIV+ (HLA-A2.1+) individuals.
authors.affiliation: Laboratory of Tumor Cell Biology, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: F
authors.initials: F
authors.lastname: di Marzo Veronese
authors.forename: D
authors.initials: D
authors.lastname: Arnott
authors.forename: V
authors.initials: V
authors.lastname: Barnaba
authors.forename: D J
authors.initials: DJ
authors.lastname: Loftus
authors.forename: K
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
authors.forename: S
authors.initials: S
authors.lastname: Salemi
authors.forename: C
authors.initials: C
authors.lastname: Mastroianni
authors.forename: A
authors.initials: A
authors.lastname: Sette
authors.forename: J
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: D F
authors.initials: DF
authors.lastname: Hunt
authors.forename: E
authors.initials: E
authors.lastname: Appella
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008285:Major Histocompatibility Complex; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016596:Vinculin / Q000096:biosynthesis* / Q000276:immunology / Q000302:isolation & purification; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology
chemical_list: D015789:HLA-A2 Antigen; D010455:Peptides; D014764:Viral Proteins; D016596:Vinculin