Transfer of T cell surface molecules to dendritic cells upon CD4+ T cell priming involves two distinct mechanisms

J Immunol. 2008 Sep 15;181(6):3965-73. doi: 10.4049/jimmunol.181.6.3965.

Abstract

Activation of CD4(+) T cells by APCs occurs by multiple Ag recognition events including the exchange of costimulatory signals and cytokines. Additionally, the T cells acquire APC-derived surface molecules. Herein, we describe for the first time the transfer of human and murine T cell surface receptors to APCs after Ag-specific interaction. This transfer occurs in two qualitatively different phases. The first group of molecules (e.g., CD2) derived from the T cell surface was transferred rapidly after 2 h of interaction, was strongly bound on the DC surface (acid wash-resistant), was strictly dependent on dendritic cell-T cell contact, and transferred independently of T cell activation. The second group, including the CD3/TCR complex, CD27, and OX40, was of intracellular origin, transferred later after 10-16 h in a cell-cell contact-independent fashion, was noncovalently bound, and was strictly dependent on Ag-specific T cell activation. Functionally, murine dendritic cells that received TCR molecules from OVA-specific CD4(+) T cells after Ag-specific interaction were less efficient in priming naive CD4(+) T cells of the same specificity without losing their ability for CD8(+) T cell stimulation, indicating that the transferred TCR molecules mask the Ag-bearing MHC II molecules, thereby reducing their accessibility to following Ag-specific CD4(+) T cells. While the first group of transferred T cell surface molecules might facilitate the detachment of the CD4(+) T cell from the dendritic cell during the early scanning phases, the second group could play an important immunomodulatory role in intraclonal competition of T cells for APC access, making the physical presence of CD4(+) T cells unnecessary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD2 Antigens / biosynthesis
  • CD2 Antigens / metabolism
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Communication / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Humans
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Transport / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cell Surface / metabolism*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • CD2 Antigens
  • CD3 Complex
  • Receptors, Antigen, T-Cell
  • Receptors, Cell Surface