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Association of Prolonged Survival in HLA-A2+ Progressive Multifocal Leukoencephalopathy Patients with a CTL Response Specific for a Commonly Recognized JC Virus Epitope

2002; American Association of Immunologists; Volume: 168; Issue: 1 Linguagem: Inglês

10.4049/jimmunol.168.1.499

1550-6606

Igor J. Koralnik, Renaud Du Pasquier, Marcelo J. Kuroda, Jörn E. Schmitz, Xin Dang, Yue Zheng, Michelle A. Lifton, Norman L. Letvin,

Antenna Design and Analysis

Abstract The role of JC virus (JCV)-specific CTL was explored in the immunopathogenesis of progressive multifocal leukoencephalopathy (PML). We identified a 9-aa epitope of the JCV capsid protein VP1, the VP1p100 peptide ILMWEAVTL, which is recognized by CTL of HLA-A2+ HIV+/PML survivors. We then constructed an HLA-A*0201/VP1p100 tetrameric complex that allowed us to assess by flow cytometry the PBMC of 13 PML patients and 11 control subjects for the presence of JCV-specific CTL. VP1p100-specific CTL were detected by tetramer binding in VP1p100-stimulated PBMC of five of seven (71%) PML survivors and zero of six PML progressors (p = 0.02). Two of three HIV+ patients with a leukoencephalopathy resembling PML, but with no virologic evidence of JCV infection, also had detectable VP1p100-specific CTL in their PBMC. PBMC of eight HIV+ patients with other neurologic diseases and healthy control subjects had no detectable JCV-specific CTL. These data suggest that the JCV-specific cellular immune response may be important in the containment of PML, and the tetramer-staining assay may provide a useful prognostic tool in the clinical management of these patients.