Immunodominant surface epitopes power immune evasion in the African trypanosome
Anastasia Gkeka,
Francisco Aresta-Branco,
Gianna Triller,
Evi P. Vlachou,
Monique van Straaten,
Mirjana Lilic,
Paul Dominic B. Olinares,
Kathryn Perez,
Brian T. Chait,
Renata Blatnik,
Thomas Ruppert,
Joseph P. Verdi,
C. Erec Stebbins,
F. Nina Papavasiliou
Affiliations
Anastasia Gkeka
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
Francisco Aresta-Branco
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
Gianna Triller
Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany
Evi P. Vlachou
Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany
Monique van Straaten
Division of Structural Biology of Infection and Immunity, German Cancer Research Center, 69120 Heidelberg, Germany
Mirjana Lilic
Laboratory of Structural Microbiology, the Rockefeller University, New York, NY 10065, USA
Paul Dominic B. Olinares
Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, the Rockefeller University, New York, NY 10065, USA
Kathryn Perez
Protein Expression and Purification Core Facility, EMBL Heidelberg, 69117 Heidelberg, Germany
Brian T. Chait
Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, the Rockefeller University, New York, NY 10065, USA
Renata Blatnik
Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
Thomas Ruppert
Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
Joseph P. Verdi
Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany; Panosome GmbH, 69123 Heidelberg, Germany
C. Erec Stebbins
Division of Structural Biology of Infection and Immunity, German Cancer Research Center, 69120 Heidelberg, Germany; Corresponding author
F. Nina Papavasiliou
Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany; Corresponding author
Summary: 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.
