Contribution of Glycosylation to T Cell Responses Stimulated

Mannoproteins are major antigens driving T cell responses to the opportunistic fungus Cryptococcus neoformans. To investigate the role played by mannosylation, an immuno-reactive cryptococcal mannoprotein was expressed recom-binantly in E. coli and Pichia pastoris, resulting in ungly-cosylated and mannosylated proteins, respectively. The Pichia-derived antigen stimulated stronger major histocom-patibility class II–restricted T cell responses. Moreover, re-sponses were potently inhibited if the antigen was chemically deglycosylated or if mannose receptors were blocked with mannans. Thus, mannosylation is critical for optimal T cell responses to a fungal antigen and should be taken into ac-count when vaccines to protect against mycoses are designed. Infections due to Cryptococcus neoformans and C. gattii have a predilection for persons with impaired T cell–mediated im