Autoreactive cytotoxic T lymphocytes in human immunodeficiency virus type 1-infected subjects

doi:10.1084/jem.183.6.2509

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Autoreactive cytotoxic T lymphocytes in human immunodeficiency virus type 1-infected subjects

F di Marzo Veronese, D Arnott, V Barnaba, DJ Loftus, K Sakaguchi, CB Thompson, S Salemi, C Mastroianni, A Sette, J Shabanowitz, DF Hunt and E Appella
Laboratory of Tumor Cell Biology, National Institutes of Health, Bethesda, Maryland 20892, USA.

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.
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