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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 Epitope¹

Igor J. Koralnik^2,*,, Renaud A. Du Pasquier^*,, Marcelo J. Kuroda, Jörn E. Schmitz, Xin Dang, Yue Zheng, Michelle Lifton and Norman L. Letvin

^* Neurology Department and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215

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 VP1_p100 peptide ILMWEAVTL, which is recognized by CTL of HLA-A2⁺ HIV⁺/PML survivors. We then constructed an HLA-A*0201/VP1_p100 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. VP1_p100-specific CTL were detected by tetramer binding in VP1_p100-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 VP1_p100-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.

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