Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells

Leen, Ann M.; Sili, Uluhan; Vanin, Elio F.; Jewell, Alan M.; Xie, Weidong; Vignali, Dario; Piedra, Pedro A.; Brenner, Malcolm K.; Rooney, Cliona M.

doi:10.1182/blood-2004-02-0646

Cited by 129 publications

(147 citation statements)

References 46 publications

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“…The first line was screened by using CTL assays in part, because a strong response to EBV after switching to BLCLs as APCs made ELISPOT screening difficult to interpret. Three peptides were identified in this line and two of these (SP28 and SP29) shared the overlapping sequence KPYSGTAYNAL, previously identified as being HLA-B*0702-restricted (Leen et al, 2004b). Using SP29, we confirmed that RD0407 also recognized KPYSGTAYNAL presented by B*0702.…”

Section: Minimum Peptide Identificationsupporting

confidence: 58%

“…The HLA-restriction panel indicated that one or more A*0101-restricted and DRB1*1101-restricted peptides were recognized. Review of the initial small-pool screening showed weak stimulation by SP91 and SP92, and both contain the previously identified A*0101-restricted epitope, TDLGQNLLY (Leen et al, 2004b). Insufficient cells remained for further characterization.…”

Section: Minimum Peptide Identificationmentioning

confidence: 97%

“…SP91, in contrast, stimulated CD8 + T cells when presented by A*0101. The minimal sequence TDLGQNLLY shared by SP91/SP92 has previously been demonstrated to be A*0101-restricted (Leen et al, 2004b).…”

Section: Minimum Peptide Identificationmentioning

confidence: 99%

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Generation of cytotoxic T-cell lines using overlapping pentadecapeptides derived from conserved regions of the adenovirus hexon protein

Zhu¹,

Xu²,

Tsao³

et al. 2010

Journal of General Virology

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Many of the 51 serotypes of adenovirus have been associated with clinically relevant infection. Adenovirus can disseminate rapidly in patients with a compromised immune system, such as that which occurs secondary to haematopoietic progenitor-cell transplantation. The higher rate of infection in recipients of T cell-depleted grafts and in those undergoing T cell-targeted treatment during graft versus host disease demonstrates the importance of a T-cell response in preventing disseminated infection. Studies have shown that the memory response to adenovirus is directed primarily to the hexon protein and is dominated by CD4 + T cells, probably due to the ability of the virus to block its presentation on HLA class I antigens. We have developed an approach to expand adenovirus-specific T cells using a pool of overlapping pentadecapeptides derived from selected conserved regions of hexon. We characterized responses to identify the peptides that are recognized, the responding T-cell subsets and their HLA restriction. Of eight lines that were characterized extensively, seven included both CD4 + and CD8 + T cells and each recognized between two and eight unique peptide sequences. By focusing the response on the conserved sequences of hexon, the cell lines are likely to recognize most of the serotypes responsible for clinically relevant disease. The 15 aa peptides used to prime the responses are more likely than whole virus or longer peptides to expand the less frequent CD8 + memory subset. Lines prepared by using our method may be more effective in adoptive immunotherapy protocols designed to prevent or treat disseminated adenovirus infections in high-risk patients.

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Section: Minimum Peptide Identificationsupporting

confidence: 58%

Section: Minimum Peptide Identificationmentioning

confidence: 97%

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Generation of cytotoxic T-cell lines using overlapping pentadecapeptides derived from conserved regions of the adenovirus hexon protein

Zhu¹,

Xu²,

Tsao³

et al. 2010

Journal of General Virology

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“…In contrast to EBV and CMV, HAdV-derived epitopes recognized by T cells are only recently coming to be identified. 16,17 Furthermore, HadVinfected cells may escape from recognition by the immune system through several mechanisms. 18 Evidence has been obtained that recovery of immunity after SCT is essential for the elimination of HAdV infection.…”

Section: Immunity and Hadv Infectionmentioning

confidence: 99%

Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity

Tol

Claas

Heemskerk

et al. 2005

Bone Marrow Transplant

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Summary:Human adenoviruses (HAdV) are a frequent cause of potentially fatal infections in patients after allogeneic stem cell transplantation, especially in children. Monitoring of serum/plasma by real-time quantitative PCR is a sensitive tool for the recognition of patients at risk of a potentially fatal infection and for the evaluation of the efficacy of treatment. Data from a retrospective study and from a prospective study demonstrate that recovery of immunity after transplantation is essential for the elimination of HAdV infection. The feasibility of several approaches for the manipulation of immunity in the immunocompromised host to prevent a fatal course of the infection is discussed. Bone Marrow Transplantation (2005) 35, S73-S76.

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“…This observation indicates that HD-Ad-derived peptides are being shuttled to MHC I pathway and cross-presented in context with MHC class I to induce CD8 ϩ T cell response along with presentation with MHC class II to induce CD4 ϩ T cell response. Five dominant CD8 ϩ T cell epitopes on the capsid hexon protein of adenovirus have been identified and because HD-Ad vector does indeed has the capsid proteins, it is possible that perhaps cross-presentation of these epitopes may play a role in inducing CD8 ϩ T cell responses (27). Our results indicate that perhaps CD8␣ DCs may play a role in cross-presenting HD-Ad-derived epitopes, because this subset of DC undergoes maturation within the draining MLN upon HD-Ad delivery.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Pulmonary T Cell Response to Helper-Dependent Adenoviral Vectors following Intranasal Delivery

Kushwah

Cao

2008

The Journal of Immunology

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In spite of the extensive research in the field of gene therapy, host immune responses continue to be the major barrier in translating basic research to clinical practice. Helper-dependent adenoviral (HD-Ad) vectors show great potential for pulmonary gene therapy, but the knowledge of pulmonary immune responses toward these vectors is very limited. In this study, we show that HD-Ad vectors are potent stimulators of dendritic cell (DC) maturation, thus leading to stimulation of T cell proliferation with ∼6% of naive CD4+ T cells from pulmonary mediastinal lymph node responding to HD-Ad-treated DCs. In contrast to the belief that HD-Ad vectors are unable to prime adaptive immune response, we show for the first time, through in vivo pulmonary studies in mice, that HD-Ad vectors can prime CD4+ and CD8+ T cell responses in the lung at high and substantially low doses. This indicates cross-presentation of HD-Ad-derived epitopes by DCs to prime CD8+ T cell responses. To assess the basis of pulmonary T cell response against HD-Ad vectors, we examined the response of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the lung. In response to HD-Ad delivery, there is induction of maturation in both cDC and pDC subsets, but it is the cDCs, not pDCs, that migrate rapidly to draining lymph nodes within the first 2 days after vector delivery to prime adaptive immune response against these vectors. These findings have implications for development of strategies to prevent adaptive immune responses against gene therapy vectors.

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Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells

Cited by 129 publications

References 46 publications

Generation of cytotoxic T-cell lines using overlapping pentadecapeptides derived from conserved regions of the adenovirus hexon protein

Generation of cytotoxic T-cell lines using overlapping pentadecapeptides derived from conserved regions of the adenovirus hexon protein

Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity

Characterization of Pulmonary T Cell Response to Helper-Dependent Adenoviral Vectors following Intranasal Delivery

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