Cross-Reactivity of T Lymphocytes Recognizing a Human Cytotoxic T-Lymphocyte Epitope within BK and JC Virus VP1 Polypeptides

Krymskaya, Ludmila; Sharma, Madeva C.; Martinez, Joy; Haq, W.; Huang, Eric C.; Limaye, Ajit P.; Diamond, Don J.; Lacey, Simon F.

doi:10.1128/jvi.79.17.11170-11178.2005

Cited by 85 publications

(69 citation statements)

References 44 publications

(53 reference statements)

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“…Since we did not study JCV-specific CD8 ϩ T-cell differentiation at the sites of active viral replication, such as in the brain of PML patients, we also cannot exclude the possibility of the presence of terminally differentiated CCR7 Ϫ CD45RA ϩ T EMRA cells in the central nervous system. We and others have demonstrated a cross-reactivity between the CTL epitopes JCV VP1 p36 and JCV VP1 p100 and BKV VP1 p44 and BKV VP1 p108 (5,20,30), respectively, indicating that the same population of CD8 ϩ T cell could be functionally active against these two viruses. In the present study, we had the opportunity to follow prospectively in the early phase of disease one PML patient who had the highest JCV-specific CTL response among all study subjects and whose virus-specific CD8 ϩ T cells expressed activation markers HLA-DR and CD38, which are usually seen at the time of viral replication (34).…”

Section: Discussionmentioning

confidence: 99%

“…BK virus (BKV) is a human polyomavirus that has 75% sequence homology with JCV and causes nephropathy in kidney transplant recipients. Indeed, we and others have recently demonstrated that CTL specific for the HLA-A*0201-restricted JCV VP1 p36 epitope cross-reacts with the BKV VP1 p44 epitope and that the HLA-A*0201-restricted JCV VP1 p100 epitope cross-reacts with the BKV VP1 p108 epitope (5,20,30), suggesting that this immune response against both human polyomaviruses may be mediated by the same CTL populations.…”

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confidence: 99%

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Frequency and Phenotype of JC Virus-Specific CD8⁺T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy

Lima

Marzocchetti

Autissier

et al. 2007

J Virol

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Frequency and Phenotype of JC Virus-Specific CD8⁺T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy

Lima

Marzocchetti

Autissier

et al. 2007

J Virol

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“…T cell responses to the LVGR‐encoded capsid viral protein VP1 were generally more pronounced than those to EVGR‐encoded viral proteins 30, 35, 49. Interferon γ (IFN‐γ) responses were largely derived from CD4 + T cells and, to a lesser extent, from CD8 + T cells 30, 35, 51, 52, 53. Because most of these studies used overlapping 15mer peptide pools (15mP), the contribution of individual CD8 + T cell–restricted epitopes to these responses is largely undefined.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses

Cioni

Leboeuf

Comoli

et al. 2016

American Journal of Transplantation

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Uncontrolled BK polyomavirus (BKPyV) replication in kidney transplant recipients (KTRs) causes polyomavirus‐associated nephropathy and allograft loss. Reducing immunosuppression is associated with clearing viremia and nephropathy and increasing BKPyV‐specific T cell responses in most patients; however, current immunoassays have limited sensitivity, target mostly CD4+ T cells, and largely fail to predict onset and clearance of BKPyV replication. To characterize BKPyV‐specific CD8+ T cells, bioinformatics were used to predict 9mer epitopes in the early viral gene region (EVGR) presented by 14 common HLAs in Europe and North America. Thirty‐nine EVGR epitopes were experimentally confirmed by interferon‐γ enzyme‐linked immunospot assays in at least 30% of BKPyV IgG–seropositive healthy participants. Most 9mers clustered in domains, and some were presented by more than one HLA class I, as typically seen for immunodominant epitopes. Specific T cell binding using MHC class I streptamers was demonstrated for 21 of 39 (54%) epitopes. In a prospective cohort of 118 pediatric KTRs, 19 patients protected or recovering from BKPyV viremia were experimentally tested, and 13 epitopes were validated. Single HLA mismatches were not associated with viremia, suggesting that failing immune control likely involves multiple factors including maintenance immunosuppression. Combining BKPyV load and T cell assays using immunodominant epitopes may help in evaluating risk and reducing immunosuppression and may lead to safe adoptive T cell transfer.

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“…VP1 p100 is conserved among JCPyV genotypes (112) and has sequence homology with BKPyV VP1 p108 (LLMWEAVTV, position 108-116) (122). Krymskaya et al showed that immunization of mice with BKPyV VP1 or in vitro stimulation of PBMC with BKPyV VP1 p108 results in the production of CD8+ T cells specific for BKPyV VP1 p108 and cross-recognizing JCV VP1 p100 (122). Similarly, JCPyV VP1 p36 has been identified as a conserved epitope as it is homologous to BKPyV VP1 p44 (AITEVECFL, position 44-52) (123).…”

Section: Aspects Of Jcpyv-specific Cellular Immunitymentioning

confidence: 99%

The human JC polyomavirus (JCPyV): virological background and clinical implications

Hirsch

Kardas

Kranz

et al. 2013

APMIS

142

169

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JC polyomavirus (JCPyV) was the first of now 12 PyVs detected in humans, when in 1964, PyV particles were revealed by electron microscopy in progressive multifocal leukoencephalopathy (PML) tissues. JCPyV infection is common in 35–70% of the general population, and the virus thereafter persists in the renourinary tract. One third of healthy adults asymptomatically shed JCPyV at approximately 50 000 copies/mL urine. PML is rare having an incidence of <0.3 per 100 000 person years in the general population. This increased to 2.4 per 1000 person years in HIV‐AIDS patients without combination antiretroviral therapy (cART). Recently, PML emerged in multiple sclerosis patients treated with natalizumab to 2.13 cases per 1000 patients. Natalizumab blocks α4‐integrin‐dependent lymphocyte homing to the brain suggesting that not the overall cellular immunodeficiency but local failure of brain immune surveillance is a pivotal factor for PML. Recovering JCPyV‐specific immune control, e.g., by starting cART or discontinuing natalizumab, significantly improves PML survival, but is challenged by the immune reconstitution inflammatory syndrome. Important steps of PML pathogenesis are undefined, and antiviral therapies are lacking. New clues might come from molecular and functional profiling of JCPyV and PML pathology and comparison with other replicative pathologies such as granule cell neuronopathy and (meningo‐)encephalitis, and non‐replicative JCPyV pathology possibly contributing to some malignancies. Given the increasing number of immunologically vulnerable patients, a critical reappraisal of JCPyV infection, replication and disease seems warranted.

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Cross-Reactivity of T Lymphocytes Recognizing a Human Cytotoxic T-Lymphocyte Epitope within BK and JC Virus VP1 Polypeptides

Cited by 85 publications

References 44 publications

Frequency and Phenotype of JC Virus-Specific CD8⁺T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy

Frequency and Phenotype of JC Virus-Specific CD8⁺T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy

Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses

The human JC polyomavirus (JCPyV): virological background and clinical implications

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Cross-Reactivity of T Lymphocytes Recognizing a Human Cytotoxic T-Lymphocyte Epitope within BK and JC Virus VP1 Polypeptides

Cited by 85 publications

References 44 publications

Frequency and Phenotype of JC Virus-Specific CD8+T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy

Frequency and Phenotype of JC Virus-Specific CD8+T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy

Characterization of Immunodominant BK Polyomavirus 9mer Epitope T Cell Responses

The human JC polyomavirus (JCPyV): virological background and clinical implications

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Product

Resources

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Frequency and Phenotype of JC Virus-Specific CD8⁺T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy

Frequency and Phenotype of JC Virus-Specific CD8⁺T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy