Antigen presentation between T cells drives Th17 polarization under conditions of limiting antigen
Viola L. Boccasavia, Elena R. Bovolenta, Ana Villanueva, Aldo Borroto, Clara L. Oeste, Hisse M. van Santen, Cristina Prieto, Diego Alonso‐López, Manuel D. Díaz‐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.