MANNAN-SPECIFIC IMMUNOGLOBULIN-G ANTIBODIES IN NORMAL HUMAN SERUM ACCELERATE BINDING OF C3 TO CANDIDA-ALBICANS VIA THE ALTERNATIVE COMPLEMENT PATHWAY

Candida albicans activates the classical and alternative complement pa thways, leading to deposition of opsonic complement fragments on the c ell surface. Our previous studies found that antimannan immunoglobulin G (IgG) in normal human serum (NHS) allows C. albicans to initiate th e classical pathway. The purpose of this study was to determine whethe r antimannan IgG also plays a role in initiation of the alternative pa thway. Pooled NHS was rendered free of classical pathway activity by c helation of serum Ca2+ with EGTA alone or in combination with immunoaf finity removal of antimannan antibodies. Kinetic analysis revealed a 6 -min lag in detection of C3 binding to C, albicans incubated in EGTA-c helated NHS, compared to a 12-min lag in NHS that was both EGTA chelat ed and mannan absorbed. The 12-min lag was shortened to 6 min by addit ion of affinity-purified antimannan IgG, The accelerating effect of an timannan IgG on alternative pathway initiation was dose dependent and was reproduced in a complement binding reaction consisting of six puri fied proteins of the alternative pathway. Both Fab and F(ab')(2) fragm ents of antimannan IgG facilitated alternative pathway initiation in a manner similar to that observed with intact antibody, Immunofluoresce nce analysis showed that addition of antimannan IgG to EGTA-chelated a nd mannan-absorbed serum promoted an early deposition of C3 molecules on the yeast cells but had little or no effect on distribution of the cellular sites for C3 activation. Thus, antimannan IgG antibodies play an important regulatory role in interactions between the host complem ent system and C. albicans.