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  • Antigen presentation between T cells drives Th17 polarization under conditions of limiting antigen.

Antigen presentation between T cells drives Th17 polarization under conditions of limiting antigen.

Cell reports (2021-03-18)
Viola L Boccasavia, Elena R Bovolenta, Ana Villanueva, Aldo Borroto, Clara L Oeste, Hisse M van Santen, Cristina Prieto, Diego Alonso-López, Manuel D Diaz-Muñoz, Facundo D Batista, Balbino Alarcón
ABSTRACT

T cells form immunological synapses with professional antigen-presenting cells (APCs) resulting in T cell activation and the acquisition of peptide antigen-MHC (pMHC) complexes from the plasma membrane of the APC. They thus become APCs themselves. We investigate the functional outcome of T-T cell antigen presentation by CD4 T cells and find that the antigen-presenting T cells (Tpres) predominantly differentiate into regulatory T cells (Treg), whereas T cells that have been stimulated by Tpres cells predominantly differentiate into Th17 pro-inflammatory cells. Using mice deficient in pMHC uptake by T cells, we show that T-T antigen presentation is important for the development of experimental autoimmune encephalitis and Th17 cell differentiation in vivo. By varying the professional APC:T cell ratio, we can modulate Treg versus Th17 differentiation in vitro and in vivo, suggesting that T-T antigen presentation underlies proinflammatory responses in conditions of antigen scarcity.

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