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

• Published in: Cell reports (Cambridge) Vol. 34; no. 11; p. 108861
• Main Authors: Boccasavia, Viola L., Bovolenta, Elena R., Villanueva, Ana, Borroto, Aldo, Oeste, Clara L., van Santen, Hisse M., Prieto, Cristina, Alonso-López, Diego, Diaz-Muñoz, Manuel D., Batista, Facundo D., Alarcón, Balbino
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.03.2021; Cell Press
• Subjects: Animals; Antigen Presentation - immunology; antigen presentation by T cells; Antigens - metabolism; CD28 Antigens - metabolism; Cell Differentiation - immunology; Cell Membrane - metabolism; Cell Polarity - immunology; Dendritic Cells - immunology; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Gene Expression Regulation; Genome; Histocompatibility Antigens Class II - immunology; Human health and pathology; Infectious diseases; Life Sciences; limiting antigen; Mice; Mice, Inbred C57BL; rho GTP-Binding Proteins - deficiency; rho GTP-Binding Proteins - metabolism; T-Lymphocytes, Regulatory - immunology; Th17; Th17 Cells - immunology; Transcription, Genetic; Treg; Trogocytosis; vaccine dosing; trogocytosis; antigen presentation by T cells; vaccine dosing; Th17; limiting antigen; Treg; antigen presentation by T cells
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.108861

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. [Display omitted] •CD4 T cells take up antigen/MHC complexes and present them to cognate T cells•After T-T cell antigen presentation, responding T cells differentiate into Th17•T-T antigen presentation underlies Th17 generation in autoimmunity and viral infection•Scarcity of antigen leads to Th17 differentiation, whereas abundance leads to Treg Boccasavia et al. show that T cells acquire antigen/MHC from professional antigen-presenting cells and convert themselves into presenting cells for other T cells of the same antigen specificity. Such T-T antigen presentation results in differentiation of the responding T cells into Th17 that mediate autoimmunity and responses to viral infections