Defining Criteria for Anti-Mannan Antibodies to Protect Against Candidiasis

Je, Cutler

doi:10.2174/1566524054022576

Cited by 55 publications

(41 citation statements)

References 66 publications

(83 reference statements)

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“…According to our hypothesis, upon entry of yeast into the bloodstream, the events that take place within the ensuing minute or so are critical to determining where in the body C. albicans becomes associated. Rapid complement activation promoted by protective antibody will favor the subsequent association of the fungus with host phagocytic cells, whereas a delay in complement opsonization that occurs with nonprotective antibodies or with alternative complement pathway activation (52) may result in a higher probability of C. albicans becoming associated with nonphagocyte-associated host sites (11).…”

Section: Discussionmentioning

confidence: 99%

Hybridoma Passage In Vitro May Result in Reduced Ability of Antimannan Antibody To Protect against Disseminated Candidiasis

Xin

Cutler

2006

Infect Immun

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We previously reported the enhanced resistance of monoclonal antibodies B6.1 (an immunoglobulin M [IgM]) and C3.1 (an IgG3) against experimental candidiasis. Both MAbs recognize the same fungal epitope. We have since found that a highly passaged B6.1 hybridoma (hp-B6.1) resulted in antibody that has little protective potential. The potential clinical applicability of the antibody and our interest in understanding antibody protection against candidiasis led us to investigate an explanation for this phenomenon. Antibody genetic structure of hp-B6.1, the original hybridoma clone (ori-B6.1) stored frozen since 1995, a subclone of hp-B6.1 that produces protective antibody, the IgG3-producing hybridoma, and a nonprotective IgG1-producing hybridoma were compared. Variable region gene sequences of heavy (V H ) and light chains showed genetic instability of V H chains with only the hp-B6.1; the V H sequences from ori-B6.1 and the subclone were, however, identical. Activation-induced cytidine deaminase levels were greatest in the B6.1 hybridomas, which may explain the instability. The constant region CH3 domain remained unchanged, implying normal N-glycation and complement-fixing potential, and antibody binding affinities appeared unchanged. Complement fixation assays surprisingly showed that ori-B6.1 antibody fixes C3 more rapidly than does hp-B6.1 antibody. The V H region primary structure may affect complement activation, which could explain our result. Indeed, antibody from the hp-B6.1 subclone fixed complement like antibody from ori-B6.1. These results show that the greatest protection occurs when antimannan antibodies possess the dual abilities of recognizing the appropriate carbohydrate epitope and rapidly fixing complement; loss of the latter property results in the loss of protective potential by the antibody.

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Section: Discussionmentioning

confidence: 99%

Hybridoma Passage In Vitro May Result in Reduced Ability of Antimannan Antibody To Protect against Disseminated Candidiasis

Xin

Cutler

2006

Infect Immun

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“…There are two serotypes of C. albicans (19), and both are frequently recovered from asymptomatic individuals or candidiasis patients (1,5). To determine whether the role of mannan and glucan in complement activation is similar between these two serotypes, we extended the studies described above to CA1 cells, a serotype B of C. albicans that has been used for studies of murine anti-mannan antibody-mediated protection (9) and for characterization of complement activation (28,50,51). Similar to serotype A 3153A cells, CA1 cells treated with any one of the three chemical methods lost the ability to bind to anti-mannan antibodies, but CA1 cells subject to Smith degradation displayed glucan (data not shown).…”

Section: Fig 4 Kinetics Of C3 Activation and Binding By Glucan-dispmentioning

confidence: 99%

Influence of Mannan and Glucan on Complement Activation and C3 Binding byCandida albicans

et al. 2010

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The complement system is important for host resistance to hematogenously disseminated candidiasis. However, modulation of complement activation by cell wall components of Candida albicans has not been characterized. Although intact yeast display mannan on the surface, glucan, typically located in the interior, becomes exposed during C. albicans infection. We show here the distinct effects of mannan and glucan on complement activation and opsonophagocytosis. Previous studies showed that intact cells are resistant to initiation of complement activation through the alternative pathway, and antimannan antibody reverses this resistance via an Fc-independent mechanism. The present study shows that this mannan-dependent resistance can be overcome by periodate-borohydride conversion of mannose polysaccharides to polyalcohols; cells treated with periodate-borohydride initiate the alternative pathway without the need for antibody. These observations identify an inhibitory role for intact mannan in complement activation. Next, removal of the surface-displayed mannan by acid treatment of periodate-borohydride cells exposes glucan. Glucan-displaying cells or purified ␤-glucan initiate the alternative pathway when incubated with the purified proteins of the alternative pathway alone, suggesting that C. albicans glucan is a natural activator of the alternative pathway. Finally, ingestion of mannan-displaying cells by human neutrophils requires anti-mannan antibody, whereas ingestion of glucan-displaying cells requires complement. These results demonstrate a contrasting requirement of natural antibody and complement for opsonophagocytosis of C. albicans cells displaying mannan or glucan. Thus, differential surface expression of mannan and glucan may influence recognition of C. albicans by the complement system.

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“…Both humoral and cell-mediated immunity are believed to play major roles in defense against Candida albicans (8). Cutler and co-workers (9 -11) have shown that glycoconjugates prepared from native antigen as well as monoclonal antibodies specific for this antigen afford protection in active and passive immunization protocols.…”

mentioning

confidence: 99%

Molecular Recognition of Candida albicans (1→2)-β-Mannan Oligosaccharides by a Protective Monoclonal Antibody Reveals the Immunodominance of Internal Saccharide Residues

Johnson

Cartmell

Weisser

et al. 2012

Journal of Biological Chemistry

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Defining Criteria for Anti-Mannan Antibodies to Protect Against Candidiasis

Cited by 55 publications

References 66 publications

Hybridoma Passage In Vitro May Result in Reduced Ability of Antimannan Antibody To Protect against Disseminated Candidiasis

Hybridoma Passage In Vitro May Result in Reduced Ability of Antimannan Antibody To Protect against Disseminated Candidiasis

Influence of Mannan and Glucan on Complement Activation and C3 Binding byCandida albicans

Molecular Recognition of Candida albicans (1→2)-β-Mannan Oligosaccharides by a Protective Monoclonal Antibody Reveals the Immunodominance of Internal Saccharide Residues

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