Mapping and characterization of the primary and anamnestic H-2 d-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus

Guillermina A. Melendi, Fidel Zavala, Ursula J. Buchholz, Guy Boivin, Peter L. Collins, Steven R. Kleeberger, Fernando P. Polack

Research output: Contribution to journalArticlepeer-review

Abstract

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 N 307-315 were detected during the anti-hMPV CTL response. Passive transfer of CD8+ T-cell lines against M2-181-89 and N 307-315 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.

Original languageEnglish (US)
Pages (from-to)11461-11467
Number of pages7
JournalJournal of virology
Volume81
Issue number20
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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