WordNet

a determining or causal element or factor; "education is an important determinant of ones outlook on life" (同)determiner, determinative, determining factor, causal factor
a square matrix used to solve simultaneous equations
any substance (as a toxin or enzyme) that stimulates an immune response in the body (especially the production of antibodies)
of or relating to antigens

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決定要素 / 決定力のある
抗原(生物の体内にはいって免疫体を作る物質)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/20 08:13:22」(JST)

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An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. For example, the epitope is the specific piece of the antigen that an antibody binds to. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes.

The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope.^[1] A conformational epitope is composed of discontinuous sections of the antigen's amino acid sequence. These epitopes interact with the paratope based on the 3-D surface features and shape or tertiary structure of the antigen. The proportion of epitopes that are conformational is unknown.^{[citation needed]}

By contrast, linear epitopes interact with the paratope based on their primary structure. A linear epitope is formed by a continuous sequence of amino acids from the antigen.

Function

T cell epitopes

T cell epitopes are presented on the surface of an antigen-presenting cell, where they are bound to MHC molecules. In humans, professional antigen-presenting cells are specialized to present MHC class II peptides, whereas most nucleated somatic cells present MHC class I peptides. T cell epitopes presented by MHC class I molecules are typically peptides between 8 and 11 amino acids in length, whereas MHC class II molecules present longer peptides, 13-17 amino acids in length,^[2] and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.

Cross-activity

Epitopes are sometimes cross-reactive. This property is exploited by the immune system in regulation by anti-idiotypic antibodies (originally proposed by Nobel laureate Niels Kaj Jerne). If an antibody binds to an antigen's epitope, the paratope could become the epitope for another antibody that will then bind to it. If this second antibody is of IgM class, its binding can upregulate the immune response; if the second antibody is of IgG class, its binding can downregulate the immune response.^{[citation needed]}

Epitope mapping

Epitopes can be mapped using protein microarrays, and with the ELISPOT or ELISA techniques.

MHC class I and II epitopes can be reliably predicted by computational means alone,^[3] although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy.^[4]

Epitope tags

Epitopes are often used in proteomics and the study of other gene products. Using recombinant DNA techniques genetic sequences coding for epitopes that are recognized by common antibodies can be fused to the gene. Following synthesis, the resulting epitope tag allows the antibody to find the protein or other gene product enabling lab techniques for localisation, purification, and further molecular characterisation. Common epitopes used for this purpose are Myc-tag, HA-tag, FLAG-tag, GST-tag, 6xHis^[5] and OLLAS.^[6] Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation.^[7]

References

^ Huang, J.; Honda, W. (2006). "CED: a conformational epitope database". BMC Immunology 7: 7. doi:10.1186/1471-2172-7-7. PMC 1513601. PMID 16603068. Retrieved April 8, 2010.
^ Alberts (2002). Molecular Biology of the Cell. New York: Garland Science. p. 1401.
^ Koren, E.; AS De Groot (July 7, 2007). "Clinical validation of the "in silico" prediction of immunogenicity of a human recombinant therapeutic protein". Clinical Immunology 124 (1). doi:10.1016/j.clim.2007.03.544.
^ De Groot, Anne; W. Martin (May 2009). "Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics". Clinical Immunology 131 (2). doi:10.1016/j.clim.2009.01.009.
^ Walker, John; Ralph Rapley (2008). Molecular biomethods handbook. Humana Press. p. 467. ISBN 1-60327-374-3.
^ Novus, Biologicals. "OLLAS Epitope Tag". Novus Biologicals. Retrieved 23 November 2011.
^ Zakeri, B. (2012). "Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin". Proceedings of the National Academy of Sciences 109 (12): E690–7. doi:10.1073/pnas.1115485109. PMC 3311370. PMID 22366317.

External links

Antibodies bind to conformational shapes on the surfaces of antigens (Janeway Immunobiology Section 3.8)
Antigens can bind in pockets or grooves, or on extended surfaces in the binding sites of antibodies (Janeway Immunobiology Figure 3.8)

Epitope prediction methods

LBEEP : Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor. [1]
Lbtope: Improved Method for Linear B-Cell Epitope Prediction Using Antigen’s Primary Sequence. PLoS ONE 8(5): e62216
BCEP: Prediction of B-cell epitopes using protein 3D structures.

Epitope databases

MHCBN: A database of MHC/TAP binder and T-cell epitopes
Bcipep: A database of B-cell epitopes
SYFPEITHI - First online database of T cell epitopes
IEDB - Database of T and B cell epitopes with annotation of recognition context - NIH funded
ANTIJEN - T and B cell epitope database at the Jenner institute, UK
IMGT/3Dstructure-DB - Three-dimensional structures of B and T cell epitopes with annotation of IG and TR - IMGT, Montpellier, France
SEDB: A Structural Epitope Database- Pondicheery University, DIT funded

Epitopes at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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English Journal

Tonsillectomy as a treatment for psoriasis: a review.

Wu W1, Debbaneh M, Moslehi H, Koo J, Liao W.Author information 1Department of Dermatology, Psoriasis and Skin Treatment Center, University of California, San Francisco Medical Center , San Francisco, CA , USA .AbstractPsoriasis is a chronic skin disorder that affects 1% to 3% of the general population worldwide. Streptococcal infection, especially streptococcal pharyngitis, has been shown to be a significant trigger of psoriasis in some patients, possibly by sensitizing T cells to keratin epitopes in the skin. Due to the role of the palatine tonsils as an immunological organ that may generate autoreactive T cells, tonsillectomy has been investigated as a treatment for psoriasis. Tonsillectomy originally gained acceptance in Japan as a treatment for palmoplantar pustulosis, a condition that shares features with pustular psoriasis. Subsequently, tonsillectomy has been used for the treatment of plaque psoriasis and guttate psoriasis. Recently, the first randomized, controlled clinical trial of tonsillectomy was performed. Here, we review the available evidence for the benefit of tonsillectomy as a treatment for palmoplantar pustulosis and psoriasis. We also discuss molecular studies aimed at understanding the role of tonsils in skin disease.
The Journal of dermatological treatment.J Dermatolog Treat.2014 Dec;25(6):482-6. doi: 10.3109/09546634.2013.848258. Epub 2013 Nov 27.
Psoriasis is a chronic skin disorder that affects 1% to 3% of the general population worldwide. Streptococcal infection, especially streptococcal pharyngitis, has been shown to be a significant trigger of psoriasis in some patients, possibly by sensitizing T cells to keratin epitopes in the skin. Du
PMID 24283892

Direct biosensor detection of botulinum neurotoxin endopeptidase activity in sera from patients with type A botulism.

Lévêque C1, Ferracci G2, Maulet Y3, Mazuet C4, Popoff M4, Seagar M3, El Far O3.Author information 1INSERM, UMR_S 1072, 13015 Marseille, France; Aix-Marseille Université, 13015 Marseille, France. Electronic address: christian.leveque@univ-amu.fr.2CNRS, UMR 7286, Plate-Forme de Recherche en Neurosciences PFRN, 13015 Marseille, France; Aix-Marseille Université, 13015 Marseille, France.3INSERM, UMR_S 1072, 13015 Marseille, France; Aix-Marseille Université, 13015 Marseille, France.4CNR Anaérobies et botulisme, Unité Bactéries anaérobies et toxines. Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.AbstractBotulinum neurotoxin A (BoNT/A) has intrinsic endoprotease activity specific for SNAP-25, a key protein for presynaptic neurotransmitter release. The inactivation of SNAP-25 by BoNT/A underlies botulism, a rare but potentially fatal disease. There is a crucial need for a rapid and sensitive in vitro serological test for BoNT/A to replace the current in vivo mouse bioassay. Cleavage of SNAP-25 by BoNT/A generates neo-epitopes which can be detected by binding of a monoclonal antibody (mAb10F12) and thus measured by surface plasmon resonance (SPR). We have explored two SPR assay formats, with either mAb10F12 or His6-SNAP-25 coupled to the biosensor chip. When BoNT/A was incubated with SNAP-25 in solution and the reaction products were captured on a mAb-coated chip, a sensitivity of 5fM (0.1LD50/ml serum) was obtained. However, this configuration required prior immunoprecipitation of BoNT/A. A sensitivity of 0.5fM in 10% serum (0.1 LD50/ml serum) was attained when SNAP-25 was coupled directly to the chip, followed by sequential injection of BoNT/A samples and mAb10F12 into the flow system to achieve on-chip cleavage and detection, respectively. This latter format detected BoNT/A endoprotease activity in 50-100µl serum samples from all patients (11/11) with type A botulism within 5h. No false positives occurred in sera from healthy subjects or patients with other neurological diseases. The automated chip-based procedure has excellent specificity and sensitivity, with significant advantages over the mouse bioassay in terms of rapidity, required sample volume and animal ethics.
Biosensors & bioelectronics.Biosens Bioelectron.2014 Jul 15;57:207-12. doi: 10.1016/j.bios.2014.02.015. Epub 2014 Feb 18.
Botulinum neurotoxin A (BoNT/A) has intrinsic endoprotease activity specific for SNAP-25, a key protein for presynaptic neurotransmitter release. The inactivation of SNAP-25 by BoNT/A underlies botulism, a rare but potentially fatal disease. There is a crucial need for a rapid and sensitive in vitro
PMID 24583693

A CagA-independent cluster of antigens related to the risk of noncardia gastric cancer: Associations between Helicobacter pylori antibodies and gastric adenocarcinoma explored by multiplex serology.

Song H1, Michel A, Nyrén O, Ekström AM, Pawlita M, Ye W.Author information 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.AbstractBecause of the differences in bacterial epitopes and host characteristics, infections with Helicobacter pylori (H. pylori) induce different immune responses. We explored the possibility that certain antibody response patterns are more closely linked to gastric adenocarcinoma (GAC) than others. In a Swedish population-based case-control study, serum samples were obtained from 268 cases and 222 controls, aged 40-79 years and frequency-matched according to age and sex. We measured antibodies against 17 H. pylori proteins using multiplex serology. Associations were estimated with multivariably adjusted logistic regression models, using odds ratio (OR) with 95% confidence interval (CI) as measures of relative risk. Associations were essentially confined to non-cardia GAC but did not differ significantly between intestinal and diffuse subtypes. Point estimates for all antibodies were above unity, 15 significant with top three being CagA (OR = 9.2), GroEL (6.6), HyuA (3.6). ORs were substantially attenuated in individuals with chronic atrophic gastritis. Principal component analysis identified two significant factors: a CagA-dominant factor (antibodies against CagA, VacA and Omp as prominent markers), and a non-CagA factor (antibodies against NapA and Catalase as prominent markers). Both factors showed dose-dependent associations with non-cardia GAC risk (CagA-dominant factor, highest vs. lowest quartiles, OR = 16.2 [95% CI 4.8-54.9]; non-CagA factor OR = 5.3 [95% CI 2.1-13.3]). Overall, our results confirm that serum antibodies against different H. pylori proteins are associated with the presence of non-cardia GAC. Although strongest association is detected by antibodies against CagA and covarying proteins, a pattern of antibodies unrelated to CagA is also significantly linked to the risk of non-cardia GAC.
International journal of cancer. Journal international du cancer.Int J Cancer.2014 Jun 15;134(12):2942-50. doi: 10.1002/ijc.28621. Epub 2013 Dec 3.
Because of the differences in bacterial epitopes and host characteristics, infections with Helicobacter pylori (H. pylori) induce different immune responses. We explored the possibility that certain antibody response patterns are more closely linked to gastric adenocarcinoma (GAC) than others. In a
PMID 24259284

Japanese Journal

Characterization of the carbohydrate backbone of Vibrio parahaemolyticus O6 lipopolysaccharides

一色恭徳,近藤誠一
Microbiology and Immunology 55(8), 539-551, 2011-08
… ELISA and ELISA inhibition analysis using antisera against O6 and Salmonella enterica Minnesota R595 and LPS of both strains further revealed that Kdo is not involved as an antigenic determinant of O6 LPS.2011 The Societies and Blackwell Publishing Asia Pty Ltd. 36p. …
NAID 120005518477

線虫におけるパウチマンノース型N-グリカンの機能

Schachter Harry
Trends in glycoscience and glycotechnology 21(119), 131-148, 2009-05-31
線虫には約 150 種類の N 型糖鎖の存在が判明している。本稿では，無脊椎動物に多く存在し，脊椎動物にないパウチマンノース型 N-グリカンの合成と機能について考察する。線虫の糖鎖はフコシル化とホスフォリルコリン付加により，多様性を呈しており，ホスフォリルコリンは多くの病原菌において抗原決定基として知られている。パウチマンノース型 N-グリカンの合成には，UDP-GlcNAc:α3-D-マンノシド …
NAID 10026976414

Antigenic Epitopes on Human P-glycoprotein Recognized by Autoimmune Hepatitis Autoantibody as a Case Study

Masuda Masatoshi,Mizutani Takaharu
Journal of health science 53(3), 282-290, 2007-06-01
… In this study, to determine antigenic sites, peptides on the extra-cellular loop (ECL), TMD and NBD of MDR1 were applied to ELISA with sera from 4 autoimmune hepatitis (AIH) patients and 4 normal individuals. … These results suggest that some ECL on MDR1 play a role of antigenic determinants, and TMD and NBD do not. … Personal specificity and diversity of antibodies from the AIH patients (such as Patients 3 and 4) against antigenic determinant were found. …
NAID 110006278743

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