Virology: Research and Treatment

¹Department of Medical Oncology, 1024 Curtis Building, Thomas Jefferson University, 1015 Walnut St., Philadelphia, PA 19107. ²1800 Concord Pike, AstraZeneca PLC, Wilmington, DE 19850-5437.

Abstract

JC virus-specific CD8+ cytotoxic T lymphocytes are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy. However, very few JC virus T cell epitopes restricted to MHC class I have been defined. Of the two HLA-A*0201-restricted JCV epitopes, VP1_p36 and VP1_p100, studies have shown that they are conserved T cell epitopes of polyomaviruses. The cross-recognition associated to these epitopes has complicated the efforts of understanding the dynamics of immune response to JC virus. Based on the previously identified HLA-A*0201 binding T cell epitope of Simian virus 40 T antigen P_281–289 (KCDDVLLLL) and BK virus T antigen P_558–566 (SLQNSEFLL), T cell epitopes of JC Virus T antigen P_282–290 (KCEDVFLLM) and P_557–565 (SLSCSEYLL) were identified. In this report, we demonstrated that JC Virus P_282–290 P_557–565 were able to stimulate T cell responses in healthy donors’ PBMCs and CD8+ cytotoxic T lymphocytes raised with both peptides could recognize and lyse their targets. Most importantly, there were no T cell cross-recognitions between JC Virus, BK Virus and SV40 virus. Therefore, JCV T-ag epitopes P_282–290 and P_557–565 could be better antigen epitopes compared to VP1_p36 and VP1_p100 to study the dynamics of cellular immune response to JCV in PML patients. In addition, as a HLA-A*0201 binding T cell epitope, both peptides could be a valuable component of immunotherapies aiming at increasing the cellular immune response against JCV for the treatment of progressive multifocal leukoencephalopathy.