alexa Epitope distribution in ordered and disordered protein regions. Part B - Ordered regions and disordered binding sites are targets of T- and B-cell immunity.
Immunology

Immunology

Immunome Research

Author(s): Pavlovi MD, Jandrli DR, Miti NS

Abstract Share this page

Intrinsically disordered proteins exist in highly flexible conformational states linked to different protein functions. In this work, we have presented evidence that HLA class-I- and class-II-binding T-cell epitopes, experimentally verified in several tumor-associated antigens and nuclear systemic autoantigens, are predominantly located in ordered protein regions or at disorder/order borderlines, defined by the majority of analyzed publicly available disorder predictors. We have also observed the overlapping of secondary structural elements and prevalently hydrophobic regions with T-cell epitopes in Epstein Barr Virus (EBV) nuclear antigen 1 (EBNA-1), cancer/testis antigen MAGE-A4, and Sm-B/B', U1 snRNPA (U1A) and U1-70kDa autoantigens. The results are in accordance with the clustering of the predicted HLA class-I and class-II epitopes in protein parts which encompass the consensus of ordered regions, determined by individual disorder predictors. Some HLA class-II epitopes and linear B-cell epitopes were located near the segments predicted to have elevated crystallographic B factor in EBNA-1, Sm-B/B' and U1 snRNP A proteins, suggesting that protein flexibility could influence the structural availability of epitopes. Naturally processed T-cell epitopes and linear B-cell epitopes could also be found within putative disordered binding sites, determined by "dips" in the prevalently disordered parts of prediction profiles of the majority of disorder predictors, and peaks in ANCHOR-prediction profile. Two minor antigenic regions within EBNA-1, mapped to the residues 58-85 and 398-458, encompassing putative disordered binding sites, contain epitopes connected with anti-Ro 60kDa and anti-Sm B/B' autoimmunity in systemic lupus erythematosus. One of these regions overlaps residues 395-450, identified as the binding site of USP7 (HAUSP), which regulates the EBNA-1 replication function. In Sm-B/B', one of the putative disordered binding sites (residues 114-165) encompasses the T-cell epitope 136-153, while another, residues 200-216, flanks two proline-rich B-cell epitopes (residues 190-198 and 216-222), overlapping the preferred CD2BP2-GYF-binding motif (R/K/G)XXPPGX(R/K), characteristic of splicosomal proteins. We have noticed that the same motif (residues 397-403) is mimicked in EBNA-1 and overlaps epitope 398-404, involved in anti-Sm B/B' autoimmunity. The majority of recognized T- and B-cell epitopes in analyzed autoantigens or tumor-associated antigens appertain to the ordered or transient protein structures. The congruence between certain B- and T-cell epitopes and predicted disordered binding sites or protein-binding eukaryotic motifs in the antigens participating in molecular complexes might influence the capture of antigens, their processing and subsequent presentation and immunodominance.

This article was published in J Immunol Methods and referenced in Immunome Research

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords