Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 198, Issue 3, Pages 399-410Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20022151
Keywords
antigen-presenting cells; antigen presentation; CD8-positive T lymphocytes; influenza; immunologic memory
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Funding
- NCI NIH HHS [P30 CA021765, CA21765] Funding Source: Medline
- NHLBI NIH HHS [P01 HL063925, HL63925, R01 HL069502, HL69502] Funding Source: Medline
- NIAID NIH HHS [AI04982, AI55154, R37 AI029579, F32 AI055154, AI29579] Funding Source: Medline
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The specificity of CD8(+) T cell responses can vary dramatically between primary and secondary infections. For example, NP366-374/D-b- and PA(224-233)/D-b-Specific CD8(+) T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 nice, whereas NP366-374/D-b-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/D-b epitope, whereas only dendritic cells effectively present the PA(224-233)/D-b epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366-374/D-b-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 PA(224-233)/D-b, that are poorly expressed at the site of infection. In this regard, vaccination with the PA(224-233) 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.
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