Determining the Breadth of the Respiratory Syncytial Virus-Specific T Cell Response

Daniel S McDermott; Cory J Knudson; Steven M Varga

doi:10.1128/JVI.02139-13

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Determining the Breadth of the Respiratory Syncytial Virus-Specific T Cell Response

Journal article

Open access

Peer reviewed

Determining the Breadth of the Respiratory Syncytial Virus-Specific T Cell Response

Daniel S McDermott, Cory J Knudson and Steven M Varga

Journal of virology, Vol.88(6), pp.3135-3143

03/2014

DOI: 10.1128/JVI.02139-13

PMCID: PMC3957923

PMID: 24371055

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Abstract

Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections in infants and children under the age of 5. Studies examining RSV infection in susceptible BALB/c mice indicate that both CD4 and CD8 T cells not only contribute to viral clearance but also facilitate RSV-induced disease. However, efforts to understand the mechanisms by which RSV-specific T cells mediate disease following acute RSV infection have been hampered by the lack of defined RSV-specific T cell epitopes. Using an overlapping peptide library spanning each of the RSV-derived proteins, intracellular cytokine staining for gamma interferon was utilized to identify novel RSV-specific CD4 and CD8 T cell epitopes. Five novel CD8 T cell epitopes were revealed within the RSV fusion (F) protein and glycoprotein (G). In addition, five previously unidentified CD4 T cell epitopes were discovered, including epitopes in the phosphoprotein (P), polymerase protein (L), M2-1 protein, and nucleoprotein (N). Though the initial CD4 T cell epitopes were 15 amino acids in length, synthesis of longer peptides increased the frequency of responding CD4 T cells. Our results indicate that CD4 T cell epitopes that are 17 amino acids in length result in more optimal CD4 T cell stimulation than the commonly used 15-mer peptides. IMPORTANCE Respiratory syncytial virus (RSV) is the leading cause of hospitalization for lower respiratory tract infection in children. T cells play a critical role in clearing an acute RSV infection, as well as contributing to RSV-induced disease. Here we examined the breadth of the RSV-specific T cell response, using for the first time an overlapping peptide library spanning the entire viral genome. We identified 5 new CD4 and 5 new CD8 T cell epitopes, including a CD8 T cell epitope within the G protein that was previously believed not to elicit a CD8 T cell response. Importantly, we also demonstrated that the use of longer, 17-mer peptides elicits a higher frequency of responding CD4 T cells than the more commonly used 15-mer peptides. Our results demonstrate the breadth of the CD4 and CD8 T cell response to RSV and demonstrate the importance of using longer peptides when stimulating CD4 T cell responses.

Pathogenesis and Immunity

Details

Title: Subtitle: Determining the Breadth of the Respiratory Syncytial Virus-Specific T Cell Response
Creators: Daniel S McDermott - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA
Cory J Knudson - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA
Steven M Varga - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Journal of virology, Vol.88(6), pp.3135-3143
Publisher: American Society for Microbiology
DOI: 10.1128/JVI.02139-13
PMID: 24371055
PMCID: PMC3957923
ISSN: 0022-538X
eISSN: 1098-5514
Language: English
Date published: 03/2014
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology
Record Identifier: 9984083873102771

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