B cell epitopes

The most frequent application of SPOT-synthesis has been in the preparation of peptide arrays for the identification of linear B-cell epitopes. If the protein antigen is known, a set of overlapping peptides that encompass the entire sequence can be readily synthesized and assayed for binding of antibody (Reineke et al., 1999). The individual residues critical for binding can then be determined by SPOT-synthesis of peptides containing amino acid substitutions. 

Tam IP, Lu YA. Vaccine engineering enhancement of immunogenicity of synthetic peptide vaccine related to hepatitis in chemically defined models consisting of T- and B-cell epitopes. Proc Natl Acad Sci USA 1989 86 9084. 

Partidos C, Stanley C, Steward M. The influence of orientation and number of copies of T- cell and B-cell epitopes on the specificity and affinity of antibodies induced by chimeric peptides. Eur J Immunol 1992 22 2675. 

Lett E, et al. Immunogenicity of polysaccharides conjugated to peptides containing T- and B-cell epitopes. Infect Immun 1994 62 785. 

In addition to this, virus-like particles have been generated that contain a form of HBsAg that has been modified at the N-terminus so that it can be utilized to present T- and B-cell epitopes. The fact that the VLPs remained intact suggests that this alteration did not negatively affect the antigenic properties of the protein and that a multivalent response could be made possible. 

Molina, A., Veramendi, J., and Hervas-Stnbbs, S. (2005). Indnction of nentral-izing antibodies by a tobacco chloroplast-derived vaccine based on a B cell epitope from canine parvovirns. Virology 342(2) 266-275. 

Antibodies to the principal neutralizing determinant in the HIV gpl20 V3 loop prevent infection. The -Gly-Pro-Gly-Arg- sequence from residues 312 to 315 is found in 85-90% of HIV isolates and is believed to exist in reverse-turn conformation.1117 To determine the optimum construction of our B-cell epitope, a small library of restricted-turn constructs was screened against the V3 directed MAb 50.1. Based upon our previous analysis, both the B (before binding) and A (after binding) type constructions (Scheme 50) were incorporated into the constrained B-cell epitope library. 

It is now possible to identify T-cell epitopes, which are recognized by receptor complexes on the T-lymphocyte surface, in addition to the B-cell epitopes recognized by antibodies (which are also the B-lymphocyte receptors). T-cells are stimulated by small peptide fragments of antigens produced by intracellular proteolytic processing, so problems of conformation do not arise, and syn-... 

Peptide Vaccines. Development of a peptide vaccine is derived from the identification of the immunodominant epitope of an antigen, A polypeptide based on the amino acid sequence of the epitope can then by synthesized. Preparation of a peptide vaccine has the advantage of allowing for large-scale production of a vaccine at relatively low cost. It also allows for selecting the appropriate T- or B-cell epitopes to be included in the vaccine, which may be advantageous in some cases,... 

Reynolds, S.R., Shoemaker, C.B. and Harn, D.A. (1 992) T and B cell epitope mapping of Sm23, an integral membrane protein of Schistosoma mansoni. The Journal of Immunology 149, 3995-4001. 

In a mouse model of aerosol sensitization to birch pollen we previously demonstrated that intranasal as well as oral administration of the major birch pollen allergen Bet v 1 prevented allergic sensitization, airway inflammation and airway hyperresponsiveness [28], Similar effects were achieved using hypoallergenic derivates of Bet v 1, containing the immunodominant T cell peptides but not the anaphylactogenic B cell epitopes, for intranasal tolerance induction [60],... 

The lipopeptide vaccine described in this study consists of a CD4+ helper T-cell epitope ([T]) and a B-cell epitope ([B]). These two epitopes are separated by a lysine residue (K) to which is attached the lipid moiety via two serine residues (Fig. IB). The CD4+ T-helper epitope KLIPNASLIENCTKAEL used is derived from the fusion protein of the morbillivirus canine distemper virus (34) and is recognized by T cells from BALB/c and C57BL6 mouse strains (4). The B-cell epitope is LHRH and has the sequence HWYSGLRPG. The presence of anti-LHRH antibodies can render vaccinated animals sterile. 

Olive, C., Clair, T Yarwood, P and Good, M.F. (2002) Protection of mice from group A streptococcal infection by intranasal immunisation with a peptide vaccine that contains a conserved M protein B cell epitope and lacks a T cell autoepitope. Vaccine 20(21-22), 2816-2825. 

Taouji, S., Nomura, I., Giguere, S., et al. (2004) Immunogenecity of synthetic peptides representing linear B-cell epitopes of VapA of Rhodococcus equi. Vaccine 22(9-10), 1114-1123. 

Nardin, E.H., Calvo-Calle, J.M., Oliveira, G.A., et al. (1998) Plasmodium falciparum polyoximes highly immunogenic synthetic vaccines constructed by chemos-elective ligation of repeat B-cell epitopes and a universal T-cell epitope of CS protein. Vaccine 16(6), 590-600. 

Epitopes and Their In Slllco viral and bacterial pathogens. B-cell epitopes are separated into... 

Owing to the difficulty of evaluating discontinuous epitopes, most experimentally detected epitopes are linear epitopes. Tools for prediction of linear B-cell epitopes include 3DEX, CEP, and Pepito (26-29). IEDB has collected a list of Web tools for B-cell epitope prediction (http //tools.immuneepitope.org/main/... 

To counter the low success rate of B-cell epitope prediction, MHC class II epitopes for CD4+ T cells may be emphasized when antibody response is key in vaccine design. CD4+ T-helper cells are critical to induce the activation of B cells that produce antibodies. B-cell antigens that contain significant MHC class II epitopes may outperform B-cell antigens without cognate help. An identified T-cell epitope may sometimes contain a B-cell epitope. In addition, B-cell epitopes may colocalize near or overlap MHC class II epitopes (32, 33). 

Enshell-Seijffers D, Denisov D, Groisman B et al (2003) The mapping and reconstitution of a conformational discontinuous B-cell epitope of HIV-1. J Mol Biol 334 87-101... 

Sweredoski MJ, Baldi P (2008) PEPITO improved discontinuous B-cell epitope prediction using multiple distance thresholds and half sphere exposure. Bioinformatics 24 1459-1460... 

Blythe MJ, Flower DR (2005) Benchmarking B cell epitope prediction underperformance of existing methods. Protein Sci 14 246-248... 

Reimer U (2009) Prediction of linear B-cell epitopes. Methods Mol Biol 524 335-344... 

Graham CM, Barnett BC, Hartlmayr I et al (1989) The structural requirements for class II (I-Ad)-restricted T cell recognition of influenza hemagglutinin B cell epitopes define T cell epitopes. Eur J Immunol 19 523-528... 

In Silico Models for B-Cell Epitope Recognition and Signaling... 

Key words B-cell epitopes, Linear, Conformational, Support vector machines, Hidden Markov models, Immunoinformatics... 

For decades researchers have been developing in silico models to minimize the number of experiments needed to identify or map the potential epitopes on the antigen surface. Because of the basic differences in the recognition of B- and T-cell epitopes, researchers have derived separate algorithms and tools for the two types of epitope. This chapter discusses only B-cell epitope prediction models (linear and conformational). Although they are not very different from basic B-cell epitope algorithms, T-cell epitope models have been reviewed in detail elsewhere (7, 8). 

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