Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope

I. J. Koralnik*, R. A. Du Pasquier, M. J. Kuroda, J. E. Schmitz, X. Dang, Y. Zheng, M. Lifton, N. L. Letvin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

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-Az.ast;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.

Original languageEnglish (US)
Pages (from-to)499-504
Number of pages6
JournalJournal of Immunology
Volume168
Issue number1
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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