Autoreactive cytotoxic T lymphocytes in human immunodeficiency virus type 1-infected subjects.
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.
di Marzo Veronese
F
F
Laboratory of Tumor Cell Biology, National Institutes of Health, Bethesda, Maryland 20892, USA.
Arnott
D
D
Barnaba
V
V
Loftus
D J
DJ
Sakaguchi
K
K
Thompson
C B
CB
Salemi
S
S
Mastroianni
C
C
Sette
A
A
Shabanowitz
J
J
Hunt
D F
DF
Appella
E
E
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
D015789:HLA-A2 Antigen; D010455:Peptides; D014764:Viral Proteins; D016596:Vinculin