From absolute to exquisite specificity. Reflections on the fuzzy nature of species, specificity and antigenic sites

Regenmortel, M.H.V. Van

doi:10.1016/s0022-1759(98)00069-6

Cited by 101 publications

(74 citation statements)

References 32 publications

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“…Differences in recognition by mouse and pig antibodies have been reported before (25). It is not surprising since swine antibodies are limited to the usage of the products of only one family of variable heavy genes which are homologous to the 7183 VH family of mouse antibodies (4) whereas MAb ISU25-C1 uses the most distant J558 VH family of antibodies (unpublished results), confirming that epitopes can only be defined in terms of their complementary paratopes (36). Alternatively, the nonrecognition of synthetic peptides by MAb ISU25-C1 could be a consequence of the absence of glycosylation.…”

Section: Discussionmentioning

confidence: 61%

Identification of Neutralizing and Nonneutralizing Epitopes in the Porcine Reproductive and Respiratory Syndrome Virus GP5 Ectodomain

Ostrowski¹,

Galeota

Jar

et al. 2002

J Virol

341

181

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After infection of swine with porcine reproductive and respiratory syndrome virus (PRRSV), there is a rapid rise of PRRSV-specific nonneutralizing antibodies (NNA), while neutralizing antibodies (NA) are detectable not sooner than 3 weeks later. To characterize neutralizing epitopes, we selected phages from a 12-mer phage display library using anti-PRRSV neutralizing monoclonal antibody (MAb) ISU25-C1. In addition, phages carrying peptides recognized by swine antibodies with high seroneutralizing titer were isolated after subtracting from the library those clones binding to swine anti-PRRSV serum with no neutralizing activity. Two epitopes located in the ectodomain of PRRSV GP5 were identified. One of these epitopes, which we named epitope B, was recognized both by neutralizing MAb ISU25-C1 and swine neutralizing serum (NS) but not by swine nonneutralizing serum (NNS), indicating that it is a neutralizing epitope. Epitope B is sequential, conserved among isolates, and not immunodominant. Antibodies directed against it are detected in serum late after infection. In contrast, the other epitope, which we named epitope A, is hypervariable and immunodominant. Antibodies against it appear early after infection with PRRSV. This epitope is recognized by swine NNA but is not recognized by either neutralizing MAb ISU25-C1 or swine NA, indicating that it is not involved in PRRSV neutralization. During infection with PRRSV, epitope A may act as a decoy, eliciting most of the antibodies directed to GP5 and delaying the induction of NA against epitope B for at least 3 weeks. These results are relevant to the design of vaccines against PRRSV.

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Section: Discussionmentioning

confidence: 61%

Identification of Neutralizing and Nonneutralizing Epitopes in the Porcine Reproductive and Respiratory Syndrome Virus GP5 Ectodomain

Ostrowski¹,

Galeota

Jar

et al. 2002

J Virol

341

181

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“…The existence of the two conformational substates for anti-PAH MAb that are trapped at low temperature can be rationalized through the existing models for antibody binding. As revealed by FLN spectra of 8,9,9,8,9, …”

Section: Discussionmentioning

confidence: 97%

“…However, most MAbs lack the specificity required to bind only one adduct or metabolite, so that conventional fluorescence is not always adequate for distinguishing between different antigens possessing the same parent fluorophore. Under such conditions a more specific, high-resolution technique like fluorescence line-narrowing spectroscopy (FLNS) can be used for additional selectivity [8,15]. FLNS has proven to be useful for the detection of PAH adducts and metabolites, since it can distinguish between (stereo-)isomers and between metabolites bound to different nucleophilic sites [16].…”

Section: Introductionmentioning

confidence: 99%

High-resolution flurescence spectroscopy in immunoanalysis

Grubor

2005

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“…The implication of a protective Ab with more than one epitope is noteworthy. The fuzzy nature of Ab-Ag recognition (32,33) in the case of mAb 12A1 suggests that there may be O-acetylated and de-Oacetylated epitopes that induce protection, or that this Ab can be protective or nonprotective depending on the GXM structure that is presented to it. mAb 18B7 is being evaluated as an immunotherapeutic agent for the treatment of cryptococcosis (7).…”

Section: Discussionmentioning

confidence: 99%

Unexpected Diversity in the Fine Specificity of Monoclonal Antibodies That Use the Same V Region Gene to Glucuronoxylomannan of Cryptococcus neoformans

McFadden¹,

Casadevall

2004

The Journal of Immunology

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Most mAbs to the capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans are generated from the same VH and VL gene families. Prior Ab studies have assessed protective efficacy, Id structure and binding to capsular polysaccharides, and peptide mimetics. These data have been interpreted as indicating that most mAbs to GXM have the same specificity. A new approach to Ab specificity analysis was investigated that uses genetic manipulation to generate C. neoformans variants with structurally different capsules. C. neoformans mutants expressing GXM with defective O-acetylation were isolated and complemented by the C. neoformans gene CAS1, which is necessary for the O-acetylation of GXM. The mAbs exhibited differences in their binding to the GXM from these mutant strains, indicating previously unsuspected differences in specificity. Analysis of three closely related IgMs revealed that one (mAb 12A1) bound to an epitope that did not require O-acetylation, another (mAb 21D2) was inhibited by O-acetylation, and the third (mAb 13F1) recognized an O-acetylation-dependent conformational epitope. Furthermore, an IgG Ab (mAb 18B7) in clinical development retained binding to de-O-acetylated polysaccharide; however, greater binding was observed to O-acetylated GXM. Our findings suggest that microbial genetic techniques can provide a new approach for epitope mapping of polysaccharide-binding Abs and suggest that this method may applicable for studying the antigenic complexity of polysaccharide Ags in other capsulated microorganisms.

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From absolute to exquisite specificity. Reflections on the fuzzy nature of species, specificity and antigenic sites

Cited by 101 publications

References 32 publications

Identification of Neutralizing and Nonneutralizing Epitopes in the Porcine Reproductive and Respiratory Syndrome Virus GP5 Ectodomain

Identification of Neutralizing and Nonneutralizing Epitopes in the Porcine Reproductive and Respiratory Syndrome Virus GP5 Ectodomain

High-resolution flurescence spectroscopy in immunoanalysis

Unexpected Diversity in the Fine Specificity of Monoclonal Antibodies That Use the Same V Region Gene to Glucuronoxylomannan of Cryptococcus neoformans

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