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.
Melendi
Guillermina A
GA
Fundacion INFANT, Buenos Aires, Argentina.
Zavala
Fidel
F
Buchholz
Ursula J
UJ
Boivin
Guy
G
Collins
Peter L
PL
Kleeberger
Steven R
SR
Polack
Fernando P
FP
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