Location of ‘continuous’ antigenic determinants in the protruding regions of proteins.

Thornton, Janet M.; Edwards, Mark S.; Taylor, William R.; Barlow, David J.

doi:10.1002/j.1460-2075.1986.tb04226.x

Cited by 274 publications

(154 citation statements)

References 21 publications

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“…For example, Novotny et al (1986) demonstrated that the correlation between accessible surface area (ASA) and antigenicity is superior to the correlation between backbone flexibility and antigenicity. Thornton et al (1986) showed that antigenic sites protrude considerably from the protein surface and concluded that this property is a strong characteristic of antigenicity. Laver et al (1990) reported that epitope areas span a narrow range of 650-900Å 2 , encompassing 15-22 amino acids.…”

Section: Introductionmentioning

confidence: 99%

Computational characterization of B-cell epitopes

Rubinstein

Mayrose

Halperin

et al. 2008

Molecular Immunology

219

233

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Characterizing B-cell epitopes is a fundamental step for understanding the immunological basis of bio-recognition. To date, epitope analyses have either been based on limited structural data, or sequence data alone. In this study, our null hypothesis was that the surface of the antigen is homogeneously antigenic. To test this hypothesis, a large dataset of antibody-antigen complex structures, together with crystal structures of the native antigens, has been compiled. Computational methods were developed and applied to detect and extract physico-chemical, structural, and geometrical properties that may distinguish an epitope from the remaining antigen surface. Rigorous statistical inference was able to clearly reject the null hypothesis showing that epitopes are distinguished from the remaining antigen surface in properties such as amino acid preference, secondary structure composition, geometrical shape, and evolutionary conservation. Specifically, epitopes were found to be significantly enriched with tyrosine and tryptophan, and to show a general preference for charged and polar amino acids. Additionally, epitopes were found to show clear preference for residing on planar parts of the antigen that protrude from the surface, yet with a rugged surface shape at the atom level. The effects of complex formation on the structural properties of the antigen were also computationally characterized and it is shown that epitopes undergo compression upon antibody binding. This correlates with the finding that epitopes are enriched with unorganized secondary structure elements that render them flexible. Thus, this study extends the understanding of the underlying processes required for antibody binding, and reveals new aspects of the antibody-antigen interaction.

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Section: Introductionmentioning

confidence: 99%

Computational characterization of B-cell epitopes

Rubinstein

Mayrose

Halperin

et al. 2008

Molecular Immunology

219

233

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show abstract

“…By varying the angle, and consequently increasing the areas of the protein that are possible, the correlation does improve. When analysed critically, the correlation simply implies that all areas of globular proteins are possible Tcell epitopes, with the exception ofloops and turns -the prominent sites for B-cell recognition [13,34,35].…”

Section: Results Analyses and Discussionmentioning

confidence: 99%

“…The protrusion indices were calculated as described by Thornton et al [13]. Sequence alignments and generation of templates were carried out by methods created by Thornton and Taylor [14].…”

Section: B Methodsmentioning

confidence: 99%

Pattern Recognition Among T-Cell Epitopes

Rothbard

Townsend

Edwards

et al. 1987

Haematology and Blood Transfusion / Hämatologie Und Bluttransfusion

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“…The amino acid sequence of the measles virus F (Richardson et al, 1986) was analysed for potential B cell epitopes using algorithms to identify regions of hydrophilicity (Kyte & Doolittle, 1982), protrusion (Thornton et aL, 1986), mobility (Karplus & Schultz, 1985) and secondary structure (Wilmot & Thornton, 1988), and the following regions were identified : residues 43 to 55, 240 to 258,358 to 373,404 to 414 and 433 to 443. Of these regions, F1:404414 was chosen as the most appropriate for consideration as a potential B cell epitope because it had the properties of high hydrophilicity, high protrusion index, high mobility and the presence of a Z-turn.…”

Section: Methodsmentioning

confidence: 99%

Immune responses in mice following immunization with chimeric synthetic peptides representing B and T cell epitopes of measles virus proteins

Partidos

Stanley

Steward

1991

Journal of General Virology

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The immunogenicity of chimeric peptides produced by collinear synthesis to contain both T and B cell epitopes from the fusion protein and the haemagglutinin of measles virus was studied in mice. The T cell epitope used was from the fusion protein (residues 288 to 302), which has been shown to be promiscuous in its binding to mouse major histocompatibility complex molecules. This epitope was coupled by (i) a glycine-glycine spacer to a B cell epitope from the fusion protein (residues 404 to 414) and (ii) either its amino or carboxy terminus to a neutralizing antibody epitope from the haemagglutinin (residues 188 to 199). The results obtained show that such chimeric peptides can indeed function as complete immunogens in a range of mouse strains of different H-2 haplotype, and can induce the production of antibodies which bind to the fusion protein and to measles virus. Furthermore, it was shown that the orientation of the T cell epitope with respect to the B cell epitope had a significant effect upon the immunogenicity and antigenic specificity of the chimera. This work gives further support to the concept of rationally designed synthetic peptide vaccines.

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Location of ‘continuous’ antigenic determinants in the protruding regions of proteins.

Cited by 274 publications

References 21 publications

Computational characterization of B-cell epitopes

Computational characterization of B-cell epitopes

Pattern Recognition Among T-Cell Epitopes

Immune responses in mice following immunization with chimeric synthetic peptides representing B and T cell epitopes of measles virus proteins

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