PMID- 32038611
OWN - NLM
STAT- MEDLINE
DCOM- 20201111
LR  - 20201111
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - 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.
PG  - 3037
LID - 10.3389/fimmu.2019.03037 [doi]
LID - 3037
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-gamma 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.
CI  - Copyright (c) 2020 Heide, Wildner, Ackermann, Wittner, Marget, Sette, Sidney, 
      Jacobs and Schulze zur Wiesch.
FAU - Heide, Janna
AU  - Heide J
AD  - Infectious Diseases Unit, I. Department of Medicine, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
AD  - German Center for Infection Research (DZIF), Partner Site 
      Hamburg-Lubeck-Borstel-Riems, Hamburg, Germany.
FAU - Wildner, Nils H
AU  - Wildner NH
AD  - Infectious Diseases Unit, I. Department of Medicine, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Ackermann, Christin
AU  - Ackermann C
AD  - Infectious Diseases Unit, I. Department of Medicine, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Wittner, Melanie
AU  - Wittner M
AD  - Infectious Diseases Unit, I. Department of Medicine, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
AD  - German Center for Infection Research (DZIF), Partner Site 
      Hamburg-Lubeck-Borstel-Riems, Hamburg, Germany.
FAU - Marget, Matthias
AU  - Marget M
AD  - Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Sette, Alessandro
AU  - Sette A
AD  - Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, 
      United States.
AD  - Division of Infectious Diseases, Department of Medicine, University of 
      California, San Diego, La Jolla, CA, United States.
FAU - Sidney, John
AU  - Sidney J
AD  - Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, 
      United States.
FAU - Jacobs, Thomas
AU  - Jacobs T
AD  - Protozoa Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, 
      Germany.
FAU - Schulze Zur Wiesch, Julian
AU  - Schulze Zur Wiesch J
AD  - Infectious Diseases Unit, I. Department of Medicine, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
AD  - German Center for Infection Research (DZIF), Partner Site 
      Hamburg-Lubeck-Borstel-Riems, Hamburg, Germany.
LA  - eng
GR  - R21 AI134127/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200122
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptides)
RN  - 0 (QF116 antigen, Plasmodium falciparum)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence
MH  - Antigens, Protozoan/chemistry/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology/metabolism
MH  - Enzyme-Linked Immunospot Assay
MH  - Epitope Mapping
MH  - Epitopes, T-Lymphocyte/chemistry/*immunology
MH  - Female
MH  - Histocompatibility Antigens Class II/*immunology/metabolism
MH  - Host-Parasite Interactions/*immunology
MH  - Humans
MH  - Immunophenotyping
MH  - Malaria, Falciparum/diagnosis/*immunology/*prevention & control
MH  - Male
MH  - Middle Aged
MH  - Peptides/chemistry/immunology
MH  - Plasmodium falciparum/*immunology
MH  - Protein Binding
MH  - Young Adult
PMC - PMC6993587
OTO - NOTNLM
OT  - CD4+
OT  - CD8+
OT  - HLA binding
OT  - HLA class II
OT  - Plasmodium falciparum
OT  - Plasmodium vivax
OT  - T cell epitope
OT  - malaria
EDAT- 2020/02/11 06:00
MHDA- 2020/11/12 06:00
PMCR- 2019/01/01
CRDT- 2020/02/11 06:00
PHST- 2019/09/12 00:00 [received]
PHST- 2019/12/11 00:00 [accepted]
PHST- 2020/02/11 06:00 [entrez]
PHST- 2020/02/11 06:00 [pubmed]
PHST- 2020/11/12 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.03037 [doi]
PST - epublish
SO  - Front Immunol. 2020 Jan 22;10:3037. doi: 10.3389/fimmu.2019.03037. eCollection 
      2019.