The molecular basis for the immunogenicity of Cryptococcus neoformans mannoproteins.
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.
Levitz
Stuart M
SM
Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA 02118, USA. slevitz@bu.edu
Specht
Charles A
CA
D000818:Animals; D003455:Cryptococcus neoformans / Q000235:genetics / Q000276:immunology*; D017261:Glycosylphosphatidylinositols / Q000737:chemistry; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D017261:Glycosylphosphatidylinositols; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C025363:mannoproteins