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Detection of EXP1-Specific CD4+ T Cell Responses Directed Against a Broad Range of Epitopes Including Two Promiscuous MHC Class II Binders During Acute Plasmodium falciparum Malaria.

Detection of EXP1-Specific CD4+ T Cell Responses Directed Against a Broad Range of Epitopes Including Two Promiscuous MHC Class II Binders During Acute Plasmodium falciparum Malaria.

Authors :
Heide, Janna
Wildner, Nils H.
Ackermann, Christin
Wittner, Melanie
Marget, Matthias
Sette, Alessandro
Sidney, John
Jacobs, Thomas
Schulze zur Wiesch, Julian
Source :
Frontiers in Immunology; 1/22/2020, Vol. 10, p1-15, 15p
Publication Year :
2020

Abstract

Background: T cells are thought to play a major role in conferring immunity against malaria. This study aimed to comprehensively define the breadth and specificity of the Plasmodium falciparum (P. falciparum) -specific CD4+ T cell response directed against the exported protein 1 (EXP1) in a cohort of patients diagnosed with acute malaria. Methods: Peripheral blood mononuclear cells of 44 patients acutely infected with P. falciparum , and of one patient infected with P. vivax , were stimulated and cultured in vitro with an overlapping set of 31 P. falciparum -specific 13-17-mer peptides covering the entire EXP1 sequence. EXP1-specific T cell responses were analyzed by ELISPOT and intracellular cytokine staining for interferon-γ production after re-stimulation with individual peptides. For further characterization of the epitopes, in silico and in vitro human leukocyte antigen (HLA) binding studies and fine mapping assays were performed. Results: We detected one or more EXP1-specific CD4+ T cell responses (mean: 1.09, range 0–5) in 47% (21/45) of our patients. Responses were directed against 15 of the 31 EXP1 peptides. Peptides EXP1-P13 (aa60-74) and P15 (aa70-85) were detected by 18% (n = 8) and 27% (n = 12) of the 45 patients screened. The optimal length, as well as the corresponding most likely HLA-restriction, of each of these two peptides was assessed. Interestingly, we also identified one CD4+ T cell response against peptide EXP1-P15 in a patient who was infected with P. vivax but not falciparum. Conclusions: This first detailed characterization of novel EXP1-specific T cell epitopes provides important information for future analysis with major histocompatibility complex-multimer technology as well as for immunomonitoring and vaccine design. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16643224
Volume :
10
Database :
Complementary Index
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
141346972
Full Text :
https://doi.org/10.3389/fimmu.2019.03037