Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses.
Nat Commun
; 10(1): 2846, 2019 06 28.
Article
em En
| MEDLINE
| ID: mdl-31253788
ABSTRACT
The magnitude of T cell responses to infection is a function of the naïve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drives optimal nucleoprotein (NP)366-374 presentation, while cross-presentation is optimal for acid polymerase (PA)224-233 presentation. The study demonstrates how assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
/
Linfócitos T Citotóxicos
/
Apresentação de Antígeno
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Infecções por Orthomyxoviridae
/
Epitopos de Linfócito T
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article