TY - JOUR AU - Crowe, SR AU - Turner, SJ AU - Miller, SC AU - Roberts, AD AU - Rappolo, RA AU - Doherty, PC AU - Ely, KH AU - Woodland, DL Y2 - 2014/05/21 Y1 - 2003/08/04 SN - 0022-1007 UR - http://hdl.handle.net/11343/26616 AB - 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. N1 - application/pdf LA - English PB - ROCKEFELLER UNIV PRESS KW - Cellular Immunology; Immune System and Allergy T1 - Differential antigen presentation regulates the changing patterns of CD8(+) T cell immunodominance in primary and secondary influenza virus infections DO - 10.1084/jem.20022151 IS - JOURNAL OF EXPERIMENTAL MEDICINE VL - 198 IS - 3 SP - 399-410 L1 - /bitstream/handle/11343/26616/116828_5470.pdf?sequence=1&isAllowed=n ER -