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

• DOI: 10.1016/j.celrep.2021.108861
• Publication Date: 2021-03-18T21:16:44Z
• Authors: 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
• Keywords: rho GTP-Binding Proteins; Encephalomyelitis, Autoimmune, Experimental; Transcription, Genetic; limiting antigen; T-Lymphocytes, Regulatory; Article; 03 medical and health sciences; CD28 Antigens; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; Animals; trogocytosis; Antigens; vaccine dosing; Antigen Presentation; 0303 health sciences; [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology; Genome; Limiting antigen; Cell Membrane; Histocompatibility Antigens Class II; Cell Polarity; Cell Differentiation; Dendritic Cells; antigen presentation by T cells; Trogocytosis; 3. Good health; Treg; Mice, Inbred C57BL; Disease Models, Animal; Gene Expression Regulation; Antigen presentation by T cells; [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases; Vaccine dosing; Th17 Cells; Th17; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology

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.