1887

Abstract

Current influenza vaccines containing primarily hypervariable haemagglutinin and neuraminidase proteins must be prepared against frequent new antigenic variants. Therefore, there is an ongoing effort to develop influenza vaccines that also elicit strong and sustained cytotoxic responses against highly conserved determinants such as the matrix (M1) protein and nucleoprotein (NP). However, their antigenic presentation properties in humans are less defined. Accordingly, we analysed MHC class I and class II presentation of endogenously processed M1 and NP in human antigen presenting cells and observed expansion of both CD8- and CD4-specific effector T lymphocytes secreting gamma interferon and tumour necrosis factor. Further enhancement of basal MHC-II antigenic presentation did not improve CD4 or CD8 T-cell quality based on cytokine production upon challenge, suggesting that endogenous M1 and NP MHC-II presentation is sufficient. These new insights about T-lymphocyte expansion following endogenous M1 and NP MHC-I and -II presentation will be important to design complementary heterosubtypic vaccination strategies.

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2011-05-01
2019-10-17
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vol. , part 5, pp. 1162 - 1171

Characterization of T lymphocytes expanded by sensitization with gp-M1 expressed by APCs

APCs gating for the human ICS analysis

Characterization of other effector arms employed by human T lymphocytes

Surface effector phenotype of T lymphocytes specific to M1 or NP, with or without enhancement of MHC-II presentation

IFN-γ secretion by NP-specific murine effector memory CD8 T lymphocytes

Percentage of amino acid similarity in (a) NP, (b) M1 and (c) HA proteins from different well-known influenza A strains and clades [Single PDF file](453 KB)



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