Comparative analysis of the ex vivo IFNgamma responses to CD8+ T cell epitopes within allelic forms of PfAMA1 in subjects with natural exposure to malaria

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dc.contributor.authorNlinwe, O.N.
dc.contributor.authorOfori, E.A.
dc.contributor.authorAkyea-Mensah, K.
dc.contributor.authorKyei-Baafour, E.
dc.contributor.authorGaneshan, H.
dc.contributor.authorBelmonte, M.
dc.contributor.authorPeters, B.
dc.contributor.authorVillasante, E.
dc.contributor.authorSedegah, M.
dc.contributor.authorAsamoah Kusi, K.
dc.date.accessioned2021-11-12T11:27:25Z
dc.date.available2021-11-12T11:27:25Z
dc.date.issued2021
dc.descriptionResearch Articleen_US
dc.description.abstractAntigen 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-γ 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-γ 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-γ 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.en_US
dc.identifier.otherhttps://doi.org/10.1371/journal.pone.0257219
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/37042
dc.language.isoenen_US
dc.publisherPLOS ONEen_US
dc.subjectAntigen polymorphismsen_US
dc.subjectmalarial antigensen_US
dc.subjectHuman leukocyte antigen (HLA)en_US
dc.subjectT cell response inductionen_US
dc.titleComparative analysis of the ex vivo IFNgamma responses to CD8+ T cell epitopes within allelic forms of PfAMA1 in subjects with natural exposure to malariaen_US
dc.typeArticleen_US

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