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Journal of Virology, October 2007, p. 11461-11467, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.02423-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mapping and Characterization of the Primary and Anamnestic H-2d-Restricted Cytotoxic T-Lymphocyte Response in Mice against Human Metapneumovirus{triangledown}

Guillermina A. Melendi,1,2,3 Fidel Zavala,3 Ursula J. Buchholz,5 Guy Boivin,6 Peter L. Collins,5 Steven R. Kleeberger,7 and Fernando P. Polack1,2,3,4*

Fundacion INFANT, Buenos Aires, Argentina,1 Department of Pediatrics, School of Medicine,2 Departments of Molecular Microbiology and Immunology,3 International Health, Johns Hopkins University, Baltimore, Maryland,4 National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland,5 Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Quebec, Quebec, Canada,6 National Institute of Environmental Health Sciences, NIH, Research Triangle, North Carolina7

Received 3 November 2006/ Accepted 18 July 2007

Cytotoxic T lymphocytes (CTLs) are important for the control of virus replication during respiratory infections. For human metapneumovirus (hMPV), an H-2d-restricted CTL epitope in the M2-2 protein has been described. In this study, we screened the hMPV F, G, N, M, M2-1, and M2-2 proteins using three independent algorithms to predict H-2d CTL epitopes in BALB/c mice. A dominant epitope (GYIDDNQSI) in positions 81 to 89 of the antitermination factor M2-1 and a subdominant epitope (SPKAGLLSL) in N307-315 were detected during the anti-hMPV CTL response. Passive transfer of CD8+ T-cell lines against M2-181-89 and N307-315 protected Rag1–/– mice against hMPV challenge. Interestingly, diversification of CTL targets to include multiple epitopes was observed after repetitive infections. A subdominant response against the previously described M2-2 epitope was detected after the third infection. An understanding of the CTL response against hMPV is important for developing preventive and therapeutic strategies against the virus.

* Corresponding author. Mailing address: Johns Hopkins University, 615 N. Wolfe Street, E5202, Baltimore, MD 21205. Phone: (443) 287-6407. Fax: (410) 955-0105. E-mail: fpolack{at}jhsph.edu

{triangledown} Published ahead of print on 1 August 2007.

Journal of Virology, October 2007, p. 11461-11467, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.02423-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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