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

Cell Rep. 2021 Mar 16;34(11):108861. doi: 10.1016/j.celrep.2021.108861.

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.

Keywords: Th17; Treg; antigen presentation by T cells; limiting antigen; trogocytosis; vaccine dosing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • 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
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / immunology*
  • Transcription, Genetic
  • Trogocytosis
  • rho GTP-Binding Proteins / deficiency
  • rho GTP-Binding Proteins / metabolism

Substances

  • Antigens
  • CD28 Antigens
  • Histocompatibility Antigens Class II
  • Rhog protein, mouse
  • rho GTP-Binding Proteins