T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus.
Infection with BK virus (BKV) induces both humoral and cellular immunity, but the viral antigens of T-antigen (T-ag) stimulating T-cell responses are largely unknown. To identify BKV-specific T cells in healthy individuals, peripheral blood lymphocytes were cultured with autologous dendritic cells (DCs) loaded with BKV lysate and T cells were screened for intracellular gamma interferon production after stimulation with an overlapping 15mer peptide library of the BKV T-ag. Among many immunogenic peptides identified, four T-ag peptides were identified as candidate major histocompatibility complex class I and II T-cell epitopes, restricted to human leukocyte antigen (HLA)-B*0702, -B*08, -DRB1*0301 and -DRB1*0901. Further, a candidate 9mer peptide, LPLMRKAYL, was confirmed to be restricted to HLA-B*0702 and -B*08. Because the polyomaviruses BKV, JC virus (JCV) and Simian virus 40 (SV40) share extensive sequence similarity in the immunogenic proteins T-ag and VP1, it was hypothesized that, in humans, these proteins contain conserved cytotoxic T-lymphocyte (CTL) target epitopes. Four HLA-restricted conserved epitopes of BKV, JCV and SV40 were identified: HLA-B*07, -B*08 and -DRB1*0901 for T-ag and -A*0201 for VP1. T cells cultured in vitro that were specific for one viral antigen recognized other conserved epitopes. CTLs generated from BKV T-ag and VP1 peptide were cytotoxic to DC targets pulsed with either BKV or JCV. Therefore, infection by one of the two viruses (BKV and JCV) could establish cross-immunity against the other. Although cross-cytotoxicity experiments were not performed with SV40, cross-recognition data from conserved antigen epitopes of polyomaviruses suggest strongly that cross-immunity might also exist among the three viruses.
Li
Jongming
J
Medical Oncology Division, Thomas Jefferson University, Philadelphia, PA, USA.
Melenhorst
Jos
J
Hematology Branch, National Heart, Lung, Blood Institute, National Institutes of Health, Bldg 10 CRC, Room 3-5330, 10 Center Drive, Bethesda, MD 20892-1202, USA.
Hensel
Nancy
N
Hematology Branch, National Heart, Lung, Blood Institute, National Institutes of Health, Bldg 10 CRC, Room 3-5330, 10 Center Drive, Bethesda, MD 20892-1202, USA.
Rezvani
Katyoun
K
Hematology Branch, National Heart, Lung, Blood Institute, National Institutes of Health, Bldg 10 CRC, Room 3-5330, 10 Center Drive, Bethesda, MD 20892-1202, USA.
Sconocchia
Giuseppe
G
Hematology Branch, National Heart, Lung, Blood Institute, National Institutes of Health, Bldg 10 CRC, Room 3-5330, 10 Center Drive, Bethesda, MD 20892-1202, USA.
Kilical
Yasemin
Y
Hematology Branch, National Heart, Lung, Blood Institute, National Institutes of Health, Bldg 10 CRC, Room 3-5330, 10 Center Drive, Bethesda, MD 20892-1202, USA.
Hou
Jean
J
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders, National Institutes of Health, Bethesda, MD, USA.
Curfman
Blanche
B
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders, National Institutes of Health, Bethesda, MD, USA.
Major
Eugene
E
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders, National Institutes of Health, Bethesda, MD, USA.
Barrett
A John
AJ
Hematology Branch, National Heart, Lung, Blood Institute, National Institutes of Health, Bldg 10 CRC, Room 3-5330, 10 Center Drive, Bethesda, MD 20892-1202, USA.
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology*; D001739:BK Virus / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D013539:Simian virus 40 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte