Strong memory CD8+ T cell responses against immunodominant and three new subdominant HLA-B27-restricted influenza A CTL epitopes following secondary infection of HLA-B27 transgenic mice.
We previously showed that the known HLA-B27-restricted influenza A epitope identified from human studies, NP.383-391, was recognized by CTLs following influenza A infection of transgenic (Tg) HLA-B27/H2 class I-deficient (H2 DKO) mice. Here, we examined the kinetics of the primary NP.383-391-specific response in Tg HLA-B27/H2 DKO mice at the site of respiratory infection, along with the profile of additional influenza A epitopes recognized. While the temporal kinetics of the Tg HLA-B27/NP.383-391-specific CD8+ T cell response paralleled the H2-D(b)/NP.366-374-specific response of non-Tg H2b mice, the magnitude was less. Using epitope prediction programs, we identified three novel B27-restricted influenza A epitopes, PB2.702-710, PB1.571-579, and PB2.368-376, recognized during both the primary and secondary response to infection. Although the secondary NP.383-391-specific response was dominant, PB1.571-579 and PB2.368-376 stimulated stronger proliferative expansion in memory T cells. Our results indicate a broader B27/influenza A CTL repertoire than previously known. Together with results for other HLA class I alleles, this information will become important in improving vaccine strategies for influenza A and other human pathogens.
Cheuk
Eve
E
Research Institute, Program in Infection, Immunity, Injury and Repair, The Hospital for Sick Children, Toronto, Canada.
Chamberlain
John W
JW
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015796:HLA-B27 Antigen; D016056:Immunodominant Epitopes; D010455:Peptides; D007371:Interferon-gamma