Immunodominant surface epitopes power immune evasion in the African trypanosome.
| Title: | Immunodominant surface epitopes power immune evasion in the African trypanosome. |
|---|---|
| Authors: | Gkeka A; Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany; Panosome GmbH, 69123 Heidelberg, Germany.; Aresta-Branco F; Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, 69120 Heidelberg, Germany.; Triller G; Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany.; Vlachou EP; Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany.; van Straaten M; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, 69120 Heidelberg, Germany.; Lilic M; Laboratory of Structural Microbiology, the Rockefeller University, New York, NY 10065, USA.; Olinares PDB; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, the Rockefeller University, New York, NY 10065, USA.; Perez K; Protein Expression and Purification Core Facility, EMBL Heidelberg, 69117 Heidelberg, Germany.; Chait BT; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, the Rockefeller University, New York, NY 10065, USA.; Blatnik R; Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.; Ruppert T; Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.; Verdi JP; Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany; Panosome GmbH, 69123 Heidelberg, Germany.; Stebbins CE; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, 69120 Heidelberg, Germany. Electronic address: e.stebbins@dkfz-heidelberg.de.; Papavasiliou FN; Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany. Electronic address: n.papavasiliou@dkfz-heidelberg.de. |
| Source: | Cell reports [Cell Rep] 2023 Mar 28; Vol. 42 (3), pp. 112262. Date of Electronic Publication: 2023 Mar 20. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| MeSH Terms: | Trypanosoma* ; Trypanosoma brucei brucei*; Animals ; Immunodominant Epitopes ; Immune Evasion ; Variant Surface Glycoproteins, Trypanosoma ; Antigenic Variation ; Epitopes ; Mammals |
| Abstract: | The African trypanosome survives the immune response of its mammalian host by antigenic variation of its major surface antigen (the variant surface glycoprotein or VSG). Here we describe the antibody repertoires elicited by different VSGs. We show that the repertoires are highly restricted and are directed predominantly to distinct epitopes on the surface of the VSGs. They are also highly discriminatory; minor alterations within these exposed epitopes confer antigenically distinct properties to these VSGs and elicit different repertoires. We propose that the patterned and repetitive nature of the VSG coat focuses host immunity to a restricted set of immunodominant epitopes per VSG, eliciting a highly stereotyped response, minimizing cross-reactivity between different VSGs and facilitating prolonged immune evasion through epitope variation.; (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests F.N.P., C.E.S., and J.P.V. report being shareholders of Panosome GmbH. F.N.P. and C.E.S. report being the managing directors of Panosome GmbH. |
| Grant Information: | P41 GM109824 United States GM NIGMS NIH HHS; P41 GM103314 United States GM NIGMS NIH HHS |
| Contributed Indexing: | Keywords: African trypanosome; CP: Immunology; antibody repertoires; antigenic variation; host-pathogen interactions; immune evasion; immunodominance; immunogenic epitopes; post-translational modification; variant surface glycoproteins |
| Substance Nomenclature: | 0 (Immunodominant Epitopes); 0 (Variant Surface Glycoproteins, Trypanosoma); 0 (Epitopes) |
| Entry Date(s): | Date Created: 20230321 Date Completed: 20230403 Latest Revision: 20230410 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.celrep.2023.112262 |
| PMID: | 36943866 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural