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In Brazil, endemic regions are primarily concentrated in the Amazon region, where most cases are attributed to Plasmodium vivax. Although malaria does not confer long-term sterilizing immunity, clinical immunity is achieved, leading to asymptomatic (ASY) infections. Assessing cellular immunity against P. vivax is challenging due to the lack of well-defined antigens. Hence, we developed a library of 310 P. vivax peptides (MPv310) to evaluate antigen-specific responses of CD4+ T cells and their memory subpopulations. The specific cytokine response, IFN-\u03b3 and TNF, and upregulation of activation markers, CD69 and CD154, were assessed in P. vivax\u2013infected individuals, including symptomatic before treatment (SY-I) patients, symptomatic after treatment (SY-T) patients, ASY individuals, and uninfected individuals. CD4+ T cells were stimulated with peptides and analyzed by flow cytometry or ELISpot. MPv310 stimulation led to increased frequencies of CD154+ and CD69+CD154+ cells in symptomatic before treatment and SY-T patients and IFN-\u03b3+TNF+ cells in SY-T patients. Cytokine response was also associated with ASY status, with higher frequencies of IFN-\u03b3+TNF+ among CD4+ T cells and of IFN-\u03b3+ in the effector memory subset. Distinct antigen-specific activation patterns were also observed among symptomatic and ASY individuals when the peptide pool was divided into smaller pools representing specific antigens. This study reveals that MPv310 and different sets of minipools stimulate CD4+ T cells in symptomatic and ASY infections, having potential to be used as a new tool to assess immune mechanisms associated with different clinical presentations of the disease and protection against malaria.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf335","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T19:38:23Z","timestamp":1777318703000},"source":"Crossref","is-referenced-by-count":0,"title":["Different clinical forms of\n                    <i>Plasmodium vivax<\/i>\n                    infection result in unique T cell epitope-specific immune responses"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-1703","authenticated-orcid":false,"given":"Camila Medeiros","family":"Costa","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia e Imunologia de Doen\u00e7as Infecciosas e Parasit\u00e1rias, Instituto Ren\u00e9 Rachou\/Fiocruz Minas , Belo Horizonte, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg\u00f3rio Guilherme","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia e Imunologia de Doen\u00e7as Infecciosas e Parasit\u00e1rias, Instituto Ren\u00e9 Rachou\/Fiocruz Minas , Belo Horizonte, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cec\u00edlia S","family":"Lindestam Arlehamn","sequence":"additional","affiliation":[{"name":"Center for Vaccine Innovation, La Jolla Institute for Immunology , La Jolla, CA,","place":["United States"]},{"name":"Department of Infectious Disease Immunology, Center for Vaccine Research, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Pereira","family":"Queiroz-Glauss","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia e Imunologia de Doen\u00e7as Infecciosas e Parasit\u00e1rias, Instituto Ren\u00e9 Rachou\/Fiocruz Minas , Belo Horizonte, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor Hugo Gon\u00e7alves","family":"Gunderman","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia e Imunologia de Doen\u00e7as Infecciosas e Parasit\u00e1rias, Instituto Ren\u00e9 Rachou\/Fiocruz Minas , Belo Horizonte, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela Mar\u00edsia Mayrink","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia e Imunologia de Doen\u00e7as Infecciosas e Parasit\u00e1rias, Instituto Ren\u00e9 Rachou\/Fiocruz Minas , Belo Horizonte, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence Rodrigues Do","family":"Amaral","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioinform\u00e1tica e An\u00e1lises Moleculares, Universidade Federal de Uberl\u00e2ndia , Patos de Minas, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhelio Batista","family":"Pereira","sequence":"additional","affiliation":[{"name":"Ambulat\u00f3rio de Mal\u00e1ria, Centro de Pesquisa em Medicina Tropical , Porto Velho, Rond\u00f4nia,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro Shugiro","family":"Tada","sequence":"additional","affiliation":[{"name":"Ambulat\u00f3rio de Mal\u00e1ria, Centro de Pesquisa em Medicina Tropical , Porto Velho, Rond\u00f4nia,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olindo Assis","family":"Martins-Filho","sequence":"additional","affiliation":[{"name":"Grupo Integrado de Biomarcadores, Instituto Ren\u00e9 Rachou\/Fiocruz Minas , Belo Horizonte, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo Tostes","family":"Gazzinelli","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Ren\u00e9 Rachou\/Fiocruz Minas , Belo Horizonte, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lis Ribeiro Do Valle","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia e Imunologia de Doen\u00e7as Infecciosas e Parasit\u00e1rias, Instituto Ren\u00e9 Rachou\/Fiocruz Minas , Belo Horizonte, Minas Gerais,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"2026042715381456700_vkaf335-B1","first-page":"695","article-title":"Asymptomatic natural human infections with the Simian Malaria Parasites Plasmodium cynomolgi and Plasmodium 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