PMID- 34506564
OWN - NLM
STAT- MEDLINE
DCOM- 20211122
LR  - 20211122
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 9
DP  - 2021
TI  - Comparative analysis of the ex vivo IFN-gamma responses to CD8+ T cell epitopes 
      within allelic forms of PfAMA1 in subjects with natural exposure to malaria.
PG  - e0257219
LID - 10.1371/journal.pone.0257219 [doi]
LID - e0257219
AB  - Antigen polymorphisms in essential malarial antigens are a key challenge to the 
      design and development of broadly effective malaria vaccines. The effect of 
      polymorphisms on antibody responses is fairly well studied while much fewer 
      studies have assessed this for T cell responses. This study investigated the 
      effect of allelic polymorphisms in the malarial antigen apical membrane antigen 1 
      (AMA1) on ex vivo T cell-specific IFN-gamma responses in subjects with lifelong 
      exposure to malaria. Human leukocyte antigen (HLA) class I-restricted peptides 
      from the 3D7 clone AMA1 were bioinformatically predicted and those with variant 
      amino acid positions used to select corresponding allelic sequences from the 7G8, 
      FVO, FC27 and tm284 parasite strains. A total of 91 AMA1 9-10mer peptides from 
      the five parasite strains were identified, synthesized, grouped into 42 allele 
      sets and used to stimulate PBMCs from seven HLA class 1-typed subjects in IFN-gamma 
      ELISpot assays. PBMCs from four of the seven subjects (57%) made positive 
      responses to 18 peptides within 12 allele sets. Fifty percent of the 18 positive 
      peptides were from the 3D7 parasite variant. Amino acid substitutions that were 
      associated with IFN-gamma response abrogation were more frequently found at positions 
      1 and 6 of the tested peptides, but substitutions did not show a clear pattern of 
      association with response abrogation. Thus, while we show some evidence of 
      polymorphisms affecting T cell response induction, other factors including TCR 
      recognition of HLA-peptide complexes may also be at play.
FAU - Nlinwe, Omarine N
AU  - Nlinwe ON
AD  - Immunology Department, Noguchi Memorial Institute for Medical Research, College 
      of Health Sciences, University of Ghana, Legon, Accra, Ghana.
FAU - Ofori, Ebenezer A
AU  - Ofori EA
AD  - Immunology Department, Noguchi Memorial Institute for Medical Research, College 
      of Health Sciences, University of Ghana, Legon, Accra, Ghana.
FAU - Akyea-Mensah, Kwadwo
AU  - Akyea-Mensah K
AD  - Immunology Department, Noguchi Memorial Institute for Medical Research, College 
      of Health Sciences, University of Ghana, Legon, Accra, Ghana.
FAU - Kyei-Baafour, Eric
AU  - Kyei-Baafour E
AD  - Immunology Department, Noguchi Memorial Institute for Medical Research, College 
      of Health Sciences, University of Ghana, Legon, Accra, Ghana.
FAU - Ganeshan, Harini
AU  - Ganeshan H
AD  - Malaria Department, Naval Medical Research Center, Silver Spring, Maryland, 
      United States of America.
AD  - Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, 
      Maryland, United States of America.
FAU - Belmonte, Maria
AU  - Belmonte M
AD  - Malaria Department, Naval Medical Research Center, Silver Spring, Maryland, 
      United States of America.
AD  - Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, 
      Maryland, United States of America.
FAU - Peters, Bjoern
AU  - Peters B
AD  - Infectious Disease and Vaccine Center, La Jolla Institute for Immunology, La 
      Jolla, California, United States of America.
FAU - Villasante, Eileen
AU  - Villasante E
AD  - Malaria Department, Naval Medical Research Center, Silver Spring, Maryland, 
      United States of America.
FAU - Sedegah, Martha
AU  - Sedegah M
AD  - Malaria Department, Naval Medical Research Center, Silver Spring, Maryland, 
      United States of America.
FAU - Kusi, Kwadwo Asamoah
AU  - Kusi KA
AUID- ORCID: 0000-0001-5483-9985
AD  - Immunology Department, Noguchi Memorial Institute for Medical Research, College 
      of Health Sciences, University of Ghana, Legon, Accra, Ghana.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210910
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Malaria Vaccines)
RN  - 0 (Peptides)
RN  - 0 (Protozoan Proteins)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Antigens, Protozoan/immunology/metabolism
MH  - CD8-Positive T-Lymphocytes/*metabolism
MH  - Epitopes, T-Lymphocyte/immunology/metabolism
MH  - Female
MH  - Humans
MH  - Malaria Vaccines/therapeutic use
MH  - Malaria, Falciparum/immunology/prevention & control
MH  - Male
MH  - Middle Aged
MH  - Peptides/metabolism
MH  - Plasmodium falciparum/immunology/pathogenicity
MH  - Protozoan Proteins/immunology/metabolism
MH  - Young Adult
PMC - PMC8432784
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/09/11 06:00
MHDA- 2021/11/23 06:00
PMCR- 2021/09/10
CRDT- 2021/09/10 17:22
PHST- 2021/06/02 00:00 [received]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/09/10 17:22 [entrez]
PHST- 2021/09/11 06:00 [pubmed]
PHST- 2021/11/23 06:00 [medline]
PHST- 2021/09/10 00:00 [pmc-release]
AID - PONE-D-21-18237 [pii]
AID - 10.1371/journal.pone.0257219 [doi]
PST - epublish
SO  - PLoS One. 2021 Sep 10;16(9):e0257219. doi: 10.1371/journal.pone.0257219. 
      eCollection 2021.