Correlation between the location of antigenic sites and the prediction of turns in proteins

Pellequer, Jean‐Luc; Westhof, Éric; Regenmortel, M.H.V. Van

doi:10.1016/0165-2478(93)90072-a

Cited by 164 publications

(123 citation statements)

References 93 publications

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…We compared the performance of the Naive Bayes classifiers using the sequence identity (NBID), PSSM profiles (NBPSSM), and dipeptide composition (NBDC) representations of the data with five propensity scale based methods [21,15,11,24,16] on the protectivity and BciPep datasets using 5-fold sequence-based cross-validation [7]. The predictive performance measured by the area under the Reciever Operating Characteristic (ROC) curve is summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Predicting Protective Linear B-Cell Epitopes Using Evolutionary Information

EL-Manzalawy

Dobbs

Honavar

2008

2008 IEEE International Conference on Bioinformatics and Biomedicine

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

“…Classical methods of identifying potential linear B-cell epitopes from antigenic sequences typically rely on the use of amino acid propensity scales [23,21,15,11,24,22,1,20,29]. However, as shown by Blythe and Flower [5], the performance of such methods is only marginally better than that of random guessing.…”

Section: Introductionmentioning

confidence: 99%

Predicting Protective Linear B-Cell Epitopes Using Evolutionary Information

EL-Manzalawy

Dobbs

Honavar

2008

2008 IEEE International Conference on Bioinformatics and Biomedicine

View full text Add to dashboard Cite

show abstract

“…B-cell epitopes have historically been recognized as hydrophilic (10,11), flexible (12), mobile (high B factor; 73, 74), surface-exposed or solvent-accessible (3,5,13,57,75), enriched with ␤-turns (14) or coils/loops (3-4, 7), and highly sequencepolymorphic (3)(4)(5). Recent three-dimensionally based studies (3-7) also show that epitopes compared with non-epitope regions are (i) enriched for polar and charged amino acids and depleted of hydrophobic amino acids, (ii) more surface-exposed than the remaining protein, (iii) more sequence polymorphic, and (iv) enriched with unorganized secondary structure elements and depleted of strands and helices (3-7).…”

Section: Discussionmentioning

confidence: 99%

Inadequate Reference Datasets Biased toward Short Non-epitopes Confound B-cell Epitope Prediction

Rahman

Chowdhury

Sachse

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

X-ray crystallography has shown that an antibody paratope typically binds 15-22 amino acids (aa) of an epitope, of which 2-5 randomly distributed amino acids contribute most of the binding energy. In contrast, researchers typically choose for B-cell epitope mapping short peptide antigens in antibody binding assays. Furthermore, short 6 -11-aa epitopes, and in particular non-epitopes, are over-represented in published B-cell epitope datasets that are commonly used for development of B-cell epitope prediction approaches from protein antigen sequences. We hypothesized that such suboptimal length peptides result in weak antibody binding and cause false-negative results. We tested the influence of peptide antigen length on antibody binding by analyzing data on more than 900 peptides used for B-cell epitope mapping of immunodominant proteins of Chlamydia spp. We demonstrate that short 7-12-aa peptides of B-cell epitopes bind antibodies poorly; thus, epitope mapping with short peptide antigens falsely classifies many B-cell epitopes as non-epitopes. We also show in published datasets of confirmed epitopes and non-epitopes a direct correlation between length of peptide antigens and antibody binding. Elimination of short, <11-aa epitope/non-epitope sequences improved datasets for evaluation of in silico B-cell epitope prediction. Achieving up to 86% accuracy, protein disorder tendency is the best indicator of B-cell epitope regions for chlamydial and published datasets. For B-cell epitope prediction, the most effective approach is plotting disorder of protein sequences with the IUPred-L scale, followed by antibody reactivity testing of 16 -30-aa peptides from peak regions. This strategy overcomes the well known inaccuracy of in silico B-cell epitope prediction from primary protein sequences.Knowledge of B-cell epitopes of proteins is essential in many fields of applied biomedical research, such as antibody diagnostics and therapeutics, vaccines, as well basic research. Laboratory methods for identification of such epitopes are time-consuming and labor-intensive. Hence, any reduction in the need for discovery and confirmatory wet-lab research by epitope prediction algorithms is highly desirable. Among in silico predictive methods from primary sequence information, epitope prediction algorithms are distinguished for their lack of reliability (1). This underperformance prompted us to examine current approaches to B-cell epitope prediction by use of extensive data on epitopes and confirmed non-epitope regions of the Chlamydia spp. proteome, accumulated in research on chlamydial molecular serology (2).Recent three-dimensional antibody-antigen complex studies (3-7) show that about 15-22-aa 2 antigen peptide residues are structurally involved in binding of epitopes to ϳ17-aa residues in antibody complementarity-determining regions (CDRs; paratopes). Among these 15-22 structural epitope residues, about 2-5 aa, termed functional residues, contribute most of the total binding energy to antibodies (6). These functional residues lie...

show abstract

“…As is widely known, immunoglobulin CDRs present a secondary -turn structure, so that peptides were cyclized by addition of a disulphide bridge between the cysteines incorporated into each chain in order to ensure maximal structural homology [20].…”

Section: Discussionmentioning

confidence: 99%

The frequent mutation Gly/Asp in CDR1H may determine a cross-reactive idiotope in anti-I cold agglutinins

Abatangelo

Plotkin

Mathov

et al. 1996

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Variable domains (VH) of all known anti i/I cold agglutinin (CA) heavy chains are codified by the VH4–21 gene. While anti‐i CAs are the expression of gene rearrangement without mutations represented by amino acid changes, anti‐I CAs present, among others, a frequent somatic mutation of Gly by Asp at position 31. The hydropathy profile calculated for the CDR1H (position 30 to position 35), as well as some adjacent positions of the heavy chain belonging to anti‐i and anti‐I antibodies, showed the conformational changes accompanying the replacement of Gly by Asp. A MoAb (LP91), which had been obtained in BALB/c mice immunized with a Fabμ fragment from a monoclonal IgMκIIIb anti‐I CA (protein KAU), proved capable of inhibiting human adult erythrocyte cryoagglutination by anti‐I CAs but not that of fetal erythrocytes by anti‐i CAs. Western blot analysis disclosed that such MoAbs recognized a sequential epitope located in the Fd fragment of all anti‐I CAs employed in this study. With the purpose of checking whether Asp31 was involved in the epitope recognized by the MoAb, two peptides, D and G, were synthesized which mimicked the CDR1H structure of anti‐I and anti‐i, respectively; the MoAb only reacted with peptide D by ELISA. Subsequent experimental results indicate that the Gly/Asp mutation could be associated with the diverse specificity presented by these autoantibodies, a change determining a characteristic epitope/idiotope, recognized by LP91 in the CDR1H.

show abstract

Correlation between the location of antigenic sites and the prediction of turns in proteins

Cited by 164 publications

References 93 publications

Predicting Protective Linear B-Cell Epitopes Using Evolutionary Information

Predicting Protective Linear B-Cell Epitopes Using Evolutionary Information

Inadequate Reference Datasets Biased toward Short Non-epitopes Confound B-cell Epitope Prediction

The frequent mutation Gly/Asp in CDR1H may determine a cross-reactive idiotope in anti-I cold agglutinins

Contact Info

Product

Resources

About