MAIT cells activate dendritic cells to promote T follicular helper cell differentiation and humoral immunity

Pankhurst, T. E.; Buick, K. H.; Lange, J. L.; Marshall, A. J.; Button, K. R.; Palmer, O. R.; Farrand, K. J.; Stewart, I. F. N.; Bird, T.; Mason, N. C.; Compton, B. J.; Comoletti, D.; Salio, M.; Painter, G. F.; Hermans, I. F.; Connor, L. M.

doi:10.1101/2022.03.31.486638

bioRxiv · 10.1101/2022.03.31.486638

MAIT cells activate dendritic cells to promote T follicular helper cell differentiation and humoral immunity

Pankhurst, T. E.·Buick, K. H.·Lange, J. L.·Marshall, A. J.·Button, K. R.·Palmer, O. R.·Farrand, K. J.·Stewart, I. F. N.·Bird, T.·Mason, N. C.·Compton, B. J.·Comoletti, D.·Salio, M.·Painter, G. F.·Hermans, I. F.·Connor, L. M.

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Abstract

Protective immune responses against respiratory pathogens, including influenza virus are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has largely been hampered by the lack of a suitable mucosal adjuvant. In this study we explore a novel class of adjuvant that harness mucosal-associated invariant T (MAIT) cells. We show evidence that intranasal immunisation of MAIT cell agonists co-administered with protein, including haemagglutinin from influenza A virus induced potent humoral immunity and immunoglobulin (Ig)A production, which protected mice against infection. MAIT cell adjuvant activity was mediated by CD40L-dependent activation of dendritic cells and subsequent priming of CD4+ T follicular helper cells. In summary, we show that MAIT cells are promising vaccine targets that can be utilised as cellular adjuvants in mucosal vaccines.

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Pankhurst, T. E., Buick, K. H., Lange, J. L., Marshall, A. J., Button, K. R., Palmer, O. R., Farrand, K. J., Stewart, I. F. N., Bird, T., Mason, N. C., Compton, B. J., Comoletti, D., Salio, M., Painter, G. F., Hermans, I. F., Connor, L. M.. 2022-04-01. MAIT cells activate dendritic cells to promote T follicular helper cell differentiation and humoral immunity. https://doi.org/10.1101/2022.03.31.486638

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