Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope.
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.
Koralnik
Igor J
IJ
Neurology Department, Beth Israel Deaconess Medical Center, RE-213B, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215. ikoralni@caregroup.harvard.edu
Du Pasquier
Renaud A
RA
Kuroda
Marcelo J
MJ
Schmitz
Jörn E
JE
Dang
Xin
X
Zheng
Yue
Y
Lifton
Michelle
M
Letvin
Norman L
NL
D000956:Antigens, Viral / Q000276:immunology; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000032:analysis*; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D007700:Kinetics; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis / Q000276:immunology*; D017741:Survivors; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C062481:VP1 protein, polyomavirus