The Molecular Basis for the Immunogenicity of Cryptococcus Neoformans Mannoproteins

FEMS Yeast Res. 2006 Jun;6(4):513-24. doi: 10.1111/j.1567-1364.2006.00071.x.

Abstract

T-cell-mediated immunity is necessary for effective host defenses against infections caused by Cryptococcus neoformans. Clinical and experimental studies have identified a heterogeneous family of mannoproteins as critical cryptococcal antigens responsible for stimulating T-cell responses. The archetypal mannoprotein has a signal sequence, a functional domain, a serine/threonine-rich region and a site for attachment of a glycosylphosphatidylinositol anchor. Extensive O-mannosylation, which occurs at the serine/threonine region, facilitates recognition by mannose receptors on antigen-presenting cells, particularly dendritic cells. This results in efficient antigen uptake, processing and presentation to T cells. Inhibition of mannose receptors or deglycosylation of mannoproteins profoundly inhibits T-cell responses, demonstrating the crucial contribution of mannosylation to immunogenicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / immunology*
  • Glycosylphosphatidylinositols / chemistry
  • Humans
  • Lectins, C-Type / metabolism
  • Mannose-Binding Lectins / metabolism
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology*
  • Mice
  • Receptors, Cell Surface / metabolism
  • T-Lymphocytes / immunology*

Substances

  • Glycosylphosphatidylinositols
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • mannoproteins
  • mannose receptor