Cryptococcus neoformans is the opportunistic human-pathogenic fungus causing life-threatening meningoencephalitis in immunocompromised patients, such as patients who acquired AIDS. Several C. neoformans mannoproteins (MPs), such as MP98 and MP88, are reported as key antigens stimulating host CD4(+) T-cell response. In this study, we investigated the effect of altered structure of N-glycans assembled on MPs in interaction with host cells. The expression patterns of MP98(H) and MP88(H) proteins, the his-tagged forms without GPI-anchor, in the wild-type (WT) and various N-/O-glycosylation mutant strains indicated that MP98 is modified mainly by N-glycosylation whereas MP88 is subject to both N-glycosylation and O-mannosylation. The MP98(H) and MP88(H) proteins were purified from WT and a N-glycosylation defective mutant strain, Cnalg3Δ, in the cap59Δ mutant background to facilitate purification of secretory proteins by inhibiting capsule biosynthesis. The in vitro adhesion assay showed that both of the WT-type MPs, bearing high-mannose type N-glycans, adhered efficiently to epithelial lung cells but not to macrophage cells. The MP88(H) secreted from the alg3Δ/cap59Δ strain showed slightly decreased adhesion to lung cells compared to the WT-secreted MP88(H). However, unexpectedly, the MP98(H) protein from the alg3Δ/cap59Δ strain showed rather increased adherence to the lung cells than the WT-secreted MP98(H) protein, indicating that truncated N-glycans rather enhanced adhesion of MP98(H) to epithelial lung cells. These results indicate that altered N-glycan structures of MPs may affect the adhesion efficiency of C. neoformans in a protein-specific way.