Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections.
The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366-374/Db- and PA224-233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366-374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366-374/Db epitope, whereas only dendritic cells effectively present the PA224-233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366-374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224-233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224-233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.
Crowe
Sherry R
SR
Trudeau Institute, P.O. Box 59, Saranac Lake, NY 12983, USA.
Turner
Stephen J
SJ
Miller
Shannon C
SC
Roberts
Alan D
AD
Rappolo
Rachel A
RA
Doherty
Peter C
PC
Ely
Kenneth H
KH
Woodland
David L
DL
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D000939:Epitopes; D005260:Female; D016056:Immunodominant Epitopes / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D014758:Viral Core Proteins; C102366:nucleoprotein (366-374), influenza virus