Effect of B7-2 and CD40 signals from activated antigen-presenting cells on the ability of zwitterionic polysaccharides to induce T-Cell stimulation

Infect Immun. 2005 Apr;73(4):2184-9. doi: 10.1128/IAI.73.4.2184-2189.2005.

Abstract

Carbohydrates have been thought to stimulate immune responses independently of T cells; however, zwitterionic polysaccharides (ZPSs) from the capsules of some bacteria elicit potent CD4+-T-cell responses in vivo and in vitro. We demonstrated that HLA-DR on professional antigen-presenting cells (APCs) is required for ZPS-induced T-cell proliferation in vitro (15). Recently, it was shown that ZPSs are processed to low-molecular-weight carbohydrates by a nitric oxide-mediated mechanism in endosomes and locate in the major histocompatibility complex class II pathway (5, 15). The effect of the ZPS-mediated expression of HLA-DR and costimulatory molecules on the APC and T-cell engagement and subsequent T-cell activation has not been elucidated. Herein, we report that ZPS-mediated induction of HLA-DR-surface expression and T-cell proliferation are maximally enhanced after incubation of APCs for 8 h with ZPS. Treatment of APCs with bafilomycin A inhibits the up-regulation of ZPS-mediated HLA-DR surface expression and leads to inhibition of T-cell proliferation. Monoclonal antibodies (MAbs) to the costimulatory molecules B7-2 and CD40L specifically block ZPS-mediated T-cell activation, while a MAb to B7-1 does not. Surface expression of B7-2 and B7-1 but not of CD40 is maximally enhanced at 8 to 16 h of treatment of APCs with ZPS. The results demonstrate that the cellular immune response to ZPS depends on the translocation of HLA-DR to the cell surface and requires costimulation via B7-2 and CD40 on activated APCs. The implication is that activation of ZPS-specific T cells requires an orchestrated arrangement of both presenting and costimulatory molecules to form an immunological synapse.

Publication types

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

MeSH terms

  • Antigen-Presenting Cells / physiology*
  • Antigens, CD / physiology*
  • B7-2 Antigen
  • CD28 Antigens / physiology
  • CD40 Antigens / physiology*
  • CD40 Ligand / physiology
  • Cells, Cultured
  • HLA-DR Antigens / analysis
  • Humans
  • Lymphocyte Activation / drug effects*
  • Membrane Glycoproteins / physiology*
  • Polysaccharides, Bacterial / pharmacology*
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • B7-2 Antigen
  • CD28 Antigens
  • CD40 Antigens
  • CD86 protein, human
  • HLA-DR Antigens
  • Membrane Glycoproteins
  • Polysaccharides, Bacterial
  • CD40 Ligand