Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope. |
| |
Authors: | Igor J Koralnik Renaud A Du Pasquier Marcelo J Kuroda J?rn E Schmitz Xin Dang Yue Zheng Michelle Lifton Norman L Letvin |
| |
Affiliation: | Neurology Department, Beth Israel Deaconess Medical Center, RE-213B, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215. ikoralni@caregroup.harvard.edu |
| |
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 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. |
| |
Keywords: | |
|
|