Mapping and characterization of the primary and anamnestic H-2(d)-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus.
Cytotoxic T lymphocytes (CTLs) are important for the control of virus replication during respiratory infections. For human metapneumovirus (hMPV), an H-2(d)-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-2(d) 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 M2-1(81-89) 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.
Fundacion INFANT, Buenos Aires, Argentina.
Guillermina A
GA
Melendi
Fidel
F
Zavala
Ursula J
UJ
Buchholz
Guy
G
Boivin
Peter L
PL
Collins
Steven R
SR
Kleeberger
Fernando P
FP
Polack
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D018604:Epitope Mapping; D000939:Epitopes; D006183:H-2 Antigens / Q000276:immunology*; D006801:Humans; D029121:Metapneumovirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
D000939:Epitopes; D006183:H-2 Antigens