Volume 60, Issue 2 pp. 113-122

Rapid effector function of circulating CD4+ T cells specific for immunodominant regions of the conserved serine/threonine kinase found in Streptococcus pneumoniae (StkP) in healthy adults

Aamir Aslam

Aamir Aslam

MRC Human Immunology Unit, Oxford NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

Clinical Immunology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK

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Aaron Mason

Aaron Mason

MRC Human Immunology Unit, Oxford NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

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Sophie Zemenides

Sophie Zemenides

MRC Human Immunology Unit, Oxford NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

Clinical Immunology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK

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Hsien Chan

Hsien Chan

MRC Human Immunology Unit, Oxford NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

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Linda Nováková

Linda Nováková

Cell and Molecular Microbiology Division, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

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Pavel Branny

Pavel Branny

Cell and Molecular Microbiology Division, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

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Adam Finn

Adam Finn

Department of Clinical Sciences at South Bristol, Academic Unit of Child Health, University of Bristol, Bristol, UK

Department of Cellular and Molecular Medicine, University of Bristol, Bristol, UK

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Helen Chapel

Helen Chapel

Clinical Immunology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK

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Graham S. Ogg

Graham S. Ogg

MRC Human Immunology Unit, Oxford NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

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Correspondence: Graham S. Ogg, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK. Tel.: +18 65 22 2334; fax: +18 65 22 2502; e-mail: [email protected]

Editor: Willem van Eden

Abstract

Streptococcus pneumoniae is an encapsulated bacterium that causes significant global morbidity and mortality. There is emerging evidence that T cells contribute to the immunity that protects humans from S. pneumoniae-associated disease. However, no T-cell epitopes have been identified as yet in this bacterium and there are no data that address the functional nature of T cells specific for pneumococcal-derived epitopes. We sought to define T-cell epitopes in the conserved serine/threonine kinase, found in S. pneumoniae (StkP) and to investigate specific interferon γ (IFN-γ) production resulting from such T-cell activation in healthy donors. We were able to detect the activation of T cells in response to pneumococcal whole-cell antigen or StkP-derived peptides in all 15 individuals. We found that the majority of the T-cell responses were directed against the extracellular, penicillin-binding protein and serine/threonine kinase-associated domains. We proceeded to characterize the immunodominant epitope in detail and observed HLA-DRB1*1501 restriction. This is the first study that has identified T-cell responses to peptides derived from a protein from S. pneumoniae and has shown that in healthy adults, specific T cells have rapid IFN-γ production compatible with effector cell differentiation. The use of such T-cell epitopes will aid in the future monitoring of T-cell responses to both S. pneumoniae infection and vaccination in humans.

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