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Journal of Virology, February 2004, p. 1775-1781, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1775-1781.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Identification of a Common HLA-DP4-Restricted T-Cell Epitope in the Conserved Region of the Respiratory Syncytial Virus G Protein

L. de Waal,1 S. Yüksel,1 A. H. Brandenburg,1,{dagger} J. P. M. Langedijk,2 K. Sintnicolaas,3 G. M. G. M. Verjans,1 A. D. M. E. Osterhaus,1 and R. L. de Swart1*

Department of Virology, Erasmus MC,1 Pepscan BV, Lelystad,2 Sanquin Blood Bank South West Region, RotterdamThe Netherlands3

Received 31 July 2003/ Accepted 22 October 2003

The cellular immune response to respiratory syncytial virus (RSV) is important in both protection and immunopathogenesis. In contrast to HLA class I, HLA class II-restricted RSV-specific T-cell epitopes have not been identified. Here, we describe the generation and characterization of two human RSV-specific CD4+-T-cell clones (TCCs) associated with type 0-like cytokine profiles. TCC 1 was specific for the matrix protein and restricted over HLA-DPB1*1601, while TCC 2 was specific for the attachment protein G and restricted over either HLA-DPB1*0401 or -0402. Interestingly, the latter epitope is conserved in both RSV type A and B viruses. Given the high allele frequencies of HLA-DPB1*0401 and -0402 worldwide, this epitope could be widely recognized and boosted by recurrent RSV infections. Indeed, peptide stimulation of peripheral blood mononuclear cells from healthy adults resulted in the detection of specific responses in 8 of 13 donors. Additional G-specific TCCs were generated from three of these cultures, which recognized the identical (n = 2) or almost identical (n = 1) HLA-DP4-restricted epitope as TCC 2. No significant differences were found between the capacities of cell lines obtained from infants with severe (n = 41) or mild (n = 46) RSV lower respiratory tract infections to function as antigen-presenting cells to the G-specific TCCs, suggesting that the severity of RSV disease is not linked to the allelic frequency of HLA-DP4. In conclusion, we have identified an RSV G-specific human T helper cell epitope restricted by the widely expressed HLA class II alleles DPB1*0401 and -0402. Its putative role in protection and/or immunopathogenesis remains to be determined.

* Corresponding author. Mailing address: Department of Virology, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. Phone: 31 10 4088280. Fax: 31 10 4089485. E-mail: r.deswart{at}erasmusmc.nl.

{dagger} Present address: Public Health Laboratory, Leeuwarden, Friesland, The Netherlands.

Journal of Virology, February 2004, p. 1775-1781, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1775-1781.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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