AUTOREACTIVE CYTOTOXIC T-LYMPHOCYTES IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED SUBJECTS

A subtractive analysis of peptides eluted from major histocompatibilit y complex (MHC) class I human histocompatibility leukocyte antigen (HL A)-A2.1 molecules purified from either human immunodeficiency virus ty pe-1 (HIV-1)-infected or uninfected cells was performed using micro hi gh-performance liquid chromatography and mass spectrometry. Three pept ides unique to infected cells were identified and found to derive from a single protein, human vinculin, a structural protein not known to b e involved in viral pathogenesis. Molecular and cytofluorometric analy ses revealed vinculin mRNA and vinculin protein overexpression in B an d T lymphocytes from HIV-1-infected individuals. Vinculin peptide-spec ific CTL activity was readily elicited from peripheral blood lymphocyt es of the majority of HLA-A2.1(+), HIV+ patients tested. Our observati ons 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.