TY - JOUR
T1 - Precursor frequency and competition dictate the HLA-A2-restricted CD8
+ T cell responses to influenza A infection and vaccination in HLA-A2.1 transgenic mice
AU - Tan, Amabel C L
AU - La Gruta, Nicole L.
AU - Zeng, Weiguang
AU - Jackson, David C.
PY - 2011/8/15
Y1 - 2011/8/15
N2 - The human HLA-A2-restricted CD8
+ T cell response to influenza A virus (IAV) is largely directed against the matrix proteinderived M1
58-66 epitope and represents an archetypal example of CD8
+ T cell immunodominance. In this study, we examined the CD8
+ T cell hierarchy to M1
58-66 and two subdominant IAV-specific epitopes: NS1
122-130 and PA
46-55 in HLA-A2
+ human subjects and HLA-A2.1 transgenic (HHD) mice. Using epitope-based lipopeptides, we show that the CD8
+ T cell hierarchy induced by IAV infection could also be induced by lipopeptide vaccination in a context outside of viral infection when the Ag load is equalized. In the HHD HLA-A2.1 mouse model, we show that the naive T cell precursor frequencies, and competition at the Ag presentation level, can predict the IAV-specific CD8
+ T cell hierarchy. Immunization of mice with subdominant epitopes alone was unable to overcome the dominance of the M1
58-66-specific response in the face of IAV challenge; however, a multiepitope vaccination strategy was most effective at generating a broad and multispecific response to infection.
AB - The human HLA-A2-restricted CD8
+ T cell response to influenza A virus (IAV) is largely directed against the matrix proteinderived M1
58-66 epitope and represents an archetypal example of CD8
+ T cell immunodominance. In this study, we examined the CD8
+ T cell hierarchy to M1
58-66 and two subdominant IAV-specific epitopes: NS1
122-130 and PA
46-55 in HLA-A2
+ human subjects and HLA-A2.1 transgenic (HHD) mice. Using epitope-based lipopeptides, we show that the CD8
+ T cell hierarchy induced by IAV infection could also be induced by lipopeptide vaccination in a context outside of viral infection when the Ag load is equalized. In the HHD HLA-A2.1 mouse model, we show that the naive T cell precursor frequencies, and competition at the Ag presentation level, can predict the IAV-specific CD8
+ T cell hierarchy. Immunization of mice with subdominant epitopes alone was unable to overcome the dominance of the M1
58-66-specific response in the face of IAV challenge; however, a multiepitope vaccination strategy was most effective at generating a broad and multispecific response to infection.
UR - http://www.scopus.com/inward/record.url?scp=80051924477&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1100664
DO - 10.4049/jimmunol.1100664
M3 - Article
C2 - 21765016
AN - SCOPUS:80051924477
SN - 0022-1767
VL - 187
SP - 1895
EP - 1902
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -