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
Standard
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. / Heide, Janna; Wildner, Nils H; Ackermann, Christin; Wittner, Melanie; Marget, Matthias; Sette, Alessandro; Sidney, John; Jacobs, Thomas; Schulze Zur Wiesch, Julian.
in: FRONT IMMUNOL, Jahrgang 10, 22.01.2020, S. 3037.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - 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
AU - Heide, Janna
AU - Wildner, Nils H
AU - Ackermann, Christin
AU - Wittner, Melanie
AU - Marget, Matthias
AU - Sette, Alessandro
AU - Sidney, John
AU - Jacobs, Thomas
AU - Schulze Zur Wiesch, Julian
N1 - Copyright © 2020 Heide, Wildner, Ackermann, Wittner, Marget, Sette, Sidney, Jacobs and Schulze zur Wiesch.
PY - 2020/1/22
Y1 - 2020/1/22
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Amino Acid Sequence
KW - Antigens, Protozoan/chemistry
KW - CD4-Positive T-Lymphocytes/immunology
KW - Enzyme-Linked Immunospot Assay
KW - Epitope Mapping
KW - Epitopes, T-Lymphocyte/chemistry
KW - Female
KW - Histocompatibility Antigens Class II/immunology
KW - Host-Parasite Interactions/immunology
KW - Humans
KW - Immunophenotyping
KW - Malaria, Falciparum/diagnosis
KW - Male
KW - Middle Aged
KW - Peptides/chemistry
KW - Plasmodium falciparum/immunology
KW - Protein Binding
KW - Young Adult
U2 - 10.3389/fimmu.2019.03037
DO - 10.3389/fimmu.2019.03037
M3 - SCORING: Journal article
C2 - 32038611
VL - 10
SP - 3037
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -