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A HCMV pp65 polypeptide promotes the expansion of CD4+ and CD8+ T cells across a wide range of HLA specificities


Provenzano, M; Sais, G; Bracci, L; Egli, A; Anselmi, M; Viehl, C T; Schaub, S; Hirsch, H H; Stroncek, D F; Marincola, F M; Spagnoli, G C (2009). A HCMV pp65 polypeptide promotes the expansion of CD4+ and CD8+ T cells across a wide range of HLA specificities. Journal of Cellular and Molecular Medicine, 13(8b):2131-2147.

Abstract

Human Cytomegalovirus (HCMV) can cause life threatening disease in infected hosts. Immunization with HLA-restricted immunodominant synthetic peptides and adoptive transfer of epitope specific T cells have been envisaged to generate or boost HCMV specific cellular immunity, thereby preventing HCMV infection or reactivation. However, induction or expansion of T cells effective against HCMV are limited by the need of utilizing peptides with defined HLA restrictions. We took advantage of a combination of seven predictive algorithms to identify immunogenic peptides of potential use in the prevention or treatment of HCMV infection or reactivation. Here we describe a pp65 derived peptide (pp65(340-355), RQYDPVAALFFFDIDL: RQY16-mer), characterized by peculiar features. First, RQY-16mer is able to stimulate HCMV pp65 specific responses in both CD4+ and CD8+ T cells, restricted by a wide range of HLA class I and class II determinants. Second, RQY-16mer is able to induce an unusually wide range of effector functions in CD4+ T cells, including proliferation, killing of autologous HCMV infected target cells and cytokine production. Third, and most importantly, the RQY-16mer is able to stimulate CD4+ and CD8+ T cell responses in pharmacologically immunosuppressed patients. These data suggest that a single reagent might qualify as synthetic immunogen for potentially large populations exposed to HCMV infection or reactivation.

Abstract

Human Cytomegalovirus (HCMV) can cause life threatening disease in infected hosts. Immunization with HLA-restricted immunodominant synthetic peptides and adoptive transfer of epitope specific T cells have been envisaged to generate or boost HCMV specific cellular immunity, thereby preventing HCMV infection or reactivation. However, induction or expansion of T cells effective against HCMV are limited by the need of utilizing peptides with defined HLA restrictions. We took advantage of a combination of seven predictive algorithms to identify immunogenic peptides of potential use in the prevention or treatment of HCMV infection or reactivation. Here we describe a pp65 derived peptide (pp65(340-355), RQYDPVAALFFFDIDL: RQY16-mer), characterized by peculiar features. First, RQY-16mer is able to stimulate HCMV pp65 specific responses in both CD4+ and CD8+ T cells, restricted by a wide range of HLA class I and class II determinants. Second, RQY-16mer is able to induce an unusually wide range of effector functions in CD4+ T cells, including proliferation, killing of autologous HCMV infected target cells and cytokine production. Third, and most importantly, the RQY-16mer is able to stimulate CD4+ and CD8+ T cell responses in pharmacologically immunosuppressed patients. These data suggest that a single reagent might qualify as synthetic immunogen for potentially large populations exposed to HCMV infection or reactivation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Urological Clinic
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:08 Feb 2010 09:38
Last Modified:03 Aug 2017 15:13
Publisher:Wiley-Blackwell
ISSN:1582-1838
Additional Information:The definitive version is available at www.blackwell-synergy.com
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/j.1582-4934.2008.00531.x
PubMed ID:19604317

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