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Journal of Virology, November 2006, p. 11209-11217, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01173-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Tracking of Peptide-Specific CD4+ T-Cell Responses after an Acute Resolving Viral Infection: a Study of Parvovirus B19{triangledown}

Victoria Kasprowicz,1,4* Adiba Isa,2 Thomas Tolfvenstam,2 Katie Jeffery,3 Paul Bowness,1 and Paul Klenerman4

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom,1 Division of Clinical Virology, Karolinska Institute, Stockholm, Sweden,2 Department of Virology, John Radcliffe Hospital, Oxford University,3 Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom4

Received 6 June 2006/ Accepted 21 August 2006

The evolution of peptide-specific CD4+ T-cell responses to acute viral infections of humans is poorly understood. We analyzed the response to parvovirus B19 (B19), a ubiquitous and clinically significant pathogen with a compact and conserved genome. The magnitude and breadth of the CD4+ T-cell response to the two B19 capsid proteins were investigated using a set of overlapping peptides and gamma interferon-specific enzyme-linked immunospot assays of peripheral blood mononuclear cells (PBMCs) from a cohort of acutely infected individuals who presented with acute arthropathy. These were compared to those for a cohort of B19-specific immunoglobulin M-negative (IgM–), IgG+ remotely infected individuals. Both cohorts of individuals were found to make broad CD4+ responses. However, while the responses following acute infection were detectable ex vivo, responses in remotely infected individuals were only detected after culture. One epitope (LASEESAFYVLEHSSFQLLG) was consistently targeted by both acutely (10/12) and remotely (6/7) infected individuals. This epitope was DRB1*1501 restricted, and a major histocompatibility complex peptide tetramer stained PBMCs from acutely infected individuals in the range of 0.003 to 0.042% of CD4+ T cells. Tetramer-positive populations were initially CD62Llo; unlike the case for B19-specific CD8+ T-cell responses, however, CD62L was reexpressed at later times, as responses remained stable or declined slowly. This first identification of B19 CD4+ T-cell epitopes, including a key immunodominant peptide, provides the tools to investigate the breadth, frequency, and functions of cellular responses to this virus in a range of specific clinical settings and gives an important reference point for analysis of peptide-specific CD4+ T cells during acute and persistent virus infections of humans.

* Corresponding author. Present address: Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129. Phone: (617) 959-2319. Fax: (617) 726-5411. E-mail: vkasprowicz{at}partners.org.

{triangledown} Published ahead of print on 30 August 2006.

Journal of Virology, November 2006, p. 11209-11217, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01173-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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