Costimulation and endogenous MHC ligands contribute to T cell recognition

Nat Immunol. 2002 Jan;3(1):42-7. doi: 10.1038/ni741. Epub 2001 Dec 3.

Abstract

To initiate an immune response, key receptor-ligand pairs must cluster in "immune synapses" at the T cell-antigen-presenting cell (APC) interface. We visualized the accumulation of a major histocompatibility complex (MHC) class II molecule, I-E(k), at a T cell-B cell interface and found it was dependent on both antigen recognition and costimulation. This suggests that costimulation-driven active transport of T cell surface molecules helps to drive immunological synapse formation. Although only agonist peptide-MHC class II (agonist pMHC class II) complexes can initiate T cell activation, endogenous pMHC class II complexes also appeared to accumulate. To test this directly, we labeled a "null" pMHC class II complex and found that, although it lacked major TCR contact residues, it could be driven into the synapse in a TCR-dependent manner. Thus, low-affinity ligands can contribute to synapse formation and T cell signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology
  • CD28 Antigens / immunology
  • Calcium Signaling
  • Cell Communication / immunology*
  • Cell Polarity
  • Cells, Cultured
  • Genes, MHC Class II
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Imaging, Three-Dimensional
  • Immunologic Capping*
  • Isoantigens / immunology*
  • Ligands
  • Luminescent Proteins / analysis
  • Luminescent Proteins / genetics
  • Lymphocyte Activation / immunology*
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Macromolecular Substances
  • Membrane Proteins / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Models, Immunological*
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Transport
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / genetics
  • Self Tolerance / immunology*
  • Transfection

Substances

  • Autoantigens
  • CD28 Antigens
  • Histocompatibility Antigens Class II
  • I-E-antigen
  • Isoantigens
  • Ligands
  • Luminescent Proteins
  • Lymphocyte Function-Associated Antigen-1
  • Macromolecular Substances
  • Membrane Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins