{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:16:37Z","timestamp":1790432197608,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K24AI113002"],"award-info":[{"award-number":["K24AI113002"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI093615"],"award-info":[{"award-number":["R01AI093615"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI089674"],"award-info":[{"award-number":["U19AI089674"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012728","name":"Frederick National Laboratory for Cancer Research","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100012728","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Variation within the HLA locus been shown to play an important role in the susceptibility to and outcomes of numerous infections, but its influence on immunity to <jats:italic>P. falciparum<\/jats:italic> malaria is unclear. Increasing evidence indicates that acquired immunity to <jats:italic>P. falciparum<\/jats:italic> is mediated in part by the cellular immune response, including NK cells, CD4 and CD8 T cells, and semi-invariant \u03b3\u03b4 T cells. HLA molecules expressed by these lymphocytes influence the epitopes recognized by <jats:italic>P. falciparum<\/jats:italic>-specific T cells, and class I HLA molecules also serve as ligands for inhibitory receptors including KIR. Here we assessed the relationship of HLA class I and II alleles to the risk of <jats:italic>P. falciparum<\/jats:italic> infection and symptomatic malaria in a cohort of 892 Ugandan children and adults followed prospectively via both active and passive surveillance. We identified two HLA class I alleles, HLA-B<jats:sup>*<\/jats:sup>53:01 and HLA-C<jats:sup>*<\/jats:sup>06:02, that were associated with a higher prevalence of <jats:italic>P. falciparum<\/jats:italic> infection. Notably, no class I or II HLA alleles were found to be associated with protection from <jats:italic>P. falciparum<\/jats:italic> parasitemia or symptomatic malaria. These findings suggest that class I HLA plays a role in the ability to restrict parasitemia, supporting an essential role for the cellular immune response in <jats:italic>P. falciparum<\/jats:italic> immunity. Our findings underscore the need for better tools to enable mechanistic studies of the T cell response to <jats:italic>P. falciparum<\/jats:italic> at the epitope level and suggest that further study of the role of HLA in regulating pre-erythrocytic stages of the <jats:italic>P. falciparum<\/jats:italic> life cycle is warranted.<\/jats:p>","DOI":"10.3389\/fimmu.2021.650028","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T06:21:15Z","timestamp":1616134875000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda"],"prefix":"10.3389","volume":"12","author":[{"given":"Jean C.","family":"Digitale","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perri 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