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Journal of Virology, January 2003, p. 980-988, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.980-988.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Identification of Immunodominant Epitopes Derived from the Respiratory Syncytial Virus Fusion Protein That Are Recognized by Human CD4 T Cells

Grada M. van Bleek,1* Martien C. Poelen,1 Robbert van der Most,2 Humphrey F. Brugghe,1 Hans A. M. Timmermans,1 Claire J. Boog,1 Peter Hoogerhout,1 Henny G. Otten,3 and Cécile A. C. M. van Els1

Laboratory for Vaccine Research, National Institute for Public Health and the Environment, Bilthoven,1 Department of Immunology, Faculty of Veterinary Medicine, University of Utrecht, Utrecht,2 Department of Hematology, University Medical Center, Utrecht, The Netherlands3

Received 26 July 2002/ Accepted 8 October 2002

Memory CD4 T-cell responses against respiratory syncytial virus (RSV) were evaluated in peripheral blood mononuclear cells of healthy blood donors with gamma interferon enzyme-linked immunospot (Elispot) assays. RSV-specific responses were detected in every donor at levels varying between 0.05 and 0.3% of CD4 T cells. For all donors tested, a considerable component of the CD4 T-cell response was directed against the fusion (F) protein of RSV. We characterized a set of 31 immunodominant antigenic peptides targeted by CD4 T cells in the context of the most prevalent HLA class II molecules within the Caucasian population. Most antigenic peptides were HLA-DR restricted, whereas two dominant DQ peptides were also identified. The antigenic peptides identified were located across the entire sequence of the F protein. Several peptides were presented by more than one major histocompatibility complex class II molecule. Furthermore, most donors recognized several F peptides. Detailed knowledge about immunodominant antigenic peptides will facilitate the ability to monitor CD4 T-cell responses in patients and the measurement of correlates of protection in vaccinated subjects.

* Corresponding author. Present address: Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center, HP KE 04.133.1, P.O. Box 85500, 3508 AB Utrecht, The Netherlands. Phone: 31 30 2503905. Fax: 31 30 2505349. E-mail: G.vanbleek{at}wkz.azu.nl.

Journal of Virology, January 2003, p. 980-988, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.980-988.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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