Antibodies Elicited by a Cryptococcus neoformans-Tetanus Toxoid Conjugate Vaccine Have the Same Specificity as Those Elicited in Infection

Casadevall, Arturo; Mukherjee, Jean; Devi, S. J. N.; Schneerson, Rachel; Robbins, John B.; Scharff, Matthew D.

doi:10.1093/infdis/165.6.1086

Cited by 217 publications

(230 citation statements)

References 36 publications

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“…For the NMR studies, the P1 peptide was synthesized by Chem Pep to include 15 N-labeled methionine and . Antibody Binding to Peptide ELISA-Polystyrene plates were first coated with 1 g/ml of streptavidin in PBS followed by blocking with 1% BSA in PBS.…”

Section: Methodsmentioning

confidence: 99%

“…NMR (30,31) were recorded using 15 N-labeled P1, P1 alone, and IgG/P1 complexes on a Bruker Avance spectrometer at 600 MHz capable of applying pulse field gradients along the z axis. Experiments done at 25°C were run as 2-h blocks, after incubating P1 with the mAbs at 4°C for 2 h, 4 h, 24 h, and 7 days.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies done in our lab using four murine mAb isotypes, IgG 1 , IgG 2a , IgG 2b , and IgG 3 suggest that the C region imposes structural constraints on the V region that alter its structure and/or ability to undergo a conformational change upon Ag binding (7,(15)(16)(17)(18). Thus, although they are identical in sequence, the V regions of this group of mAbs may have secondary structures capable of different interactions that manifest themselves as changed fine specificity.…”

mentioning

confidence: 92%

“…Despite the centrality of this observation for diverse immunological effects such as vaccine responses, isotype-restricted antibody responses, and the origin of primary and secondary responses, the molecular mechanism(s) responsible for this phenomenon are not understood. In this study, we have taken a novel approach to the problem by probing the paratope with 15 N label peptide mimetics followed by NMR spectroscopy and fluorescence emission spectroscopy. Specifically, we have explored the hypothesis that the C region imposes conformational constraints on the variable (V) region to affect paratope structure in a V region identical IgG 1 , IgG 2a , IgG 2b , and IgG 3 mAbs.…”

mentioning

confidence: 99%

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Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes

Janda

Eryilmaz

Nakouzi

et al. 2012

Journal of Biological Chemistry

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Background:The mechanism by which antibody constant region alters fine specificity is unknown. Results: Different constant regions were found to change electronic and chemical properties of the antigen-binding site. Conclusion: Constant regions can affect the energy landscape of the variable region. Significance: These results are potentially critical for understanding fast, correct immune responses at the systems level and for future immunotherapy development.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 92%

mentioning

confidence: 99%

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Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes

Janda

Eryilmaz

Nakouzi

et al. 2012

Journal of Biological Chemistry

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“…The IgM mAbs 12A1 and 13F1 have been described previously (12,13,23). IgM ascites was generated in BALB/c mice given i.p.…”

Section: Monoclonal Absmentioning

confidence: 99%

Immunoglobulin M Efficacy AgainstCryptococcus neoformans: Mechanism, Dose Dependence, and Prozone-Like Effects in Passive Protection Experiments

Taborda

Casadevall

2001

The Journal of Immunology

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The IgM mAbs 12A1 and 13F1 are protective and nonprotective, respectively, against lethal Cryptococcus neoformans infection in mice. To better understand the variables that contribute to IgM efficacy against C. neoformans, we studied the effects of inoculum size, route of infection, and Ab dose for each of these mAbs. mAb 13F1 did not prolong survival under any condition studied. mAb 12A1 prolonged survival after the administration of certain Ab doses after i.p. infection with defined inocula and promoted phagocytosis, agglutination, and the formation of inflammatory cell rings around yeast cells in vivo. Large Ab doses of mAb 12A1 resulted in either no protection or enhanced infection, consistent with a prozone-like effect. Investigation of this phenomenon revealed that the fungal cell was protected against microbicidal nitrogen-derived oxidants when large amounts of Ab were bound to the C. neoformans capsule. mAb 12A1 was opsonic in vitro for peritoneal, but not splenic or alveolar macrophages. In summary, our results indicate that IgM efficacy against C. neoformans is a function of the route of infection, inoculum, and Ab dose and is associated with its ability to promote opsonization, agglutination, and phagocytic ring formation in vivo. The occurrence of the prozone-like phenomenon implies that high Ab titers are not necessarily beneficial in assuring protection against certain pathogens and that caution should be exercised in using high Ab titer as a measure for vaccine efficacy.

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Cryptococcus neoformans differently regulates B7-1 (CD80) and B7-2 (CD86) expression on human monocytes

et al. 1998

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To induce a specific response in primary resting T cells, two signals must be provided by antigen-presenting cells (APC). The first antigen-specific signal is mediated by formation of the T cell receptor major histocompatibility complex molecule ternary complexes. The second signal is delivered by interaction of either B7-1 or B7-2 expressed by APC with CD28 or CTLA-4 on T cells. In this study, we examined the modulation of B7-1 and B7-2 molecules on human monocytes exposed to encapsulated or acapsular Cryptococcus neoformans or Candida albicans. In our experimental system, C. albicans or acapsular C. neoformans are able to induce B7-1 expression while the encapsulated yeast is a poor stimulator. A modest increase of B7-2 expression was also observed after monocyte treatment with acapsular C. neoformans or C. albicans, while the encapsulated yeast was ineffective in inducing B7-2 molecules. Kinetic analysis showed the maximum expression of B7-1 after 24 to 48 h. Addition of the opsonic IgG1 mAb 2H1 to monocytes and C. neoformans significantly increased B7-1, but not B7-2, expression. The contribution of B7-1 and B7-2 co-stimulatory (CS) molecules to cryptococcal-specific T cell activation was analyzed and a substantial inhibition of T cell proliferation was observed. In this study we provide the first demonstration of fungal interference in the regulation of CS molecules. Our results suggest a potential mechanism for poor inflammatory responses observed in C. neoformans infections.

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Antibodies Elicited by a Cryptococcus neoformans-Tetanus Toxoid Conjugate Vaccine Have the Same Specificity as Those Elicited in Infection

Cited by 217 publications

References 36 publications

Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes

Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes

Immunoglobulin M Efficacy AgainstCryptococcus neoformans: Mechanism, Dose Dependence, and Prozone-Like Effects in Passive Protection Experiments

Cryptococcus neoformans differently regulates B7-1 (CD80) and B7-2 (CD86) expression on human monocytes

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