Immunodominant surface epitopes power immune evasion in the African trypanosome

DOI: 10.1016/j.celrep.2023.112262

Authors: Anastasia Gkeka (German Cancer Research Center; University of Heidelberg) , Francisco Aresta-Branco (German Cancer Research Center) , Gianna Triller (German Cancer Research Center) , Evi P. Vlachou (German Cancer Research Center) , Monique Van Straaten (German Cancer Research Center) , Mirjana Lilic (Rockefeller Universit) , Paul Dominic B. Olinares (Rockefeller University) , Kathryn Perez (EMBL Heidelberg) , Brian T. Chait (Rockefeller University) , Renata Blatnik (Heidelberg University) , Thomas Ruppert (Heidelberg University) , Joseph P. Verdi (German Cancer Research Center; Panosome GmbH) , C. Erec Stebbins (German Cancer Research Center) , F. Nina Papavasiliou (German Cancer Research)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Reports , VOL 42

State: Published (Approved)
Published: March 2023
Diamond Proposal Number(s): 24246

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.

Journal Keywords: African trypanosome; host-pathogen interactions; variant surface glycoproteins; antigenic variation; immune evasion; immunogenic epitopes; immunodominance; antibody repertoires; post-translational modification

Diamond Keywords: Sleeping Sickness

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Other Facilities: X06DA at SLS

Added On: 28/03/2023 17:39

Discipline Tags:

Infectious Diseases Disease in the Developing World Health & Wellbeing Structural biology Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)