{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:43:44Z","timestamp":1787237024926,"version":"build-2736575974"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The changes occurring in the T cell repertoire during clinical malaria infection in children remain unknown. In this study, we undertook the first detailed comparative study of the T cell repertoire in African children with and without clinical malaria to test the hypothesis that clonotypic expansions that occur during\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    infection will contribute to the generation of a T cell repertoire that is unique to each disease state. We profiled the complementarity-determining region 3 (CDR3) of the TCR\u03b2 chain sequences from children with\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    infections (asymptomatic, uncomplicated and severe malaria) and compared these with sequences from healthy children. Interestingly, we discovered that children with symptomatic malaria have a lower TCR diversity and frequency of shared (or \u201cpublic\u201d) TCR sequences compared to asymptomatic children. Also, TCR diversity was inversely associated with parasitemia. Furthermore, by clustering TCR sequences based on their predicted antigen specificities, we identified a specificity cluster, with a 4-mer amino acid motif, that is overrepresented in the asymptomatic group compared to the diseased groups. Further investigations into this finding may help in delineating important antigenic targets for vaccine and therapeutic development. The results show that the T cell repertoire in children is altered during malaria, suggesting that exposure to\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    antigens disrupts the adaptive immune response, which is an underlying feature of the disease.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.971392","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T01:48:45Z","timestamp":1665625725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Perturbations in the T cell receptor \u03b2 repertoire during malaria infection in children: A preliminary study"],"prefix":"10.3389","volume":"13","author":[{"given":"Augustina","family":"Frimpong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Fokuo","family":"Ofori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoelnaser M.","family":"Degoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwadwo Asamoah","family":"Kusi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buri","family":"Gershom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Quartey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Kyei-Baafour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhi","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Ndifon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"B1","year":"2019"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62238-2","article-title":"Malaria vaccine technology roadmap","volume":"382","author":"Moorthy","year":"2013","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4614-8757-9_131-1","article-title":"Naturally acquired immunity (NAI)","volume-title":"Encyclopedia of malaria","author":"Doba\u00f1o","year":"2018"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.35832","article-title":"Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure","volume":"7","author":"Rodriguez-Barraquer","year":"2018","journal-title":"eLife"},{"key":"B5","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1186\/s12936-018-2410-6","article-title":"Characterization of T cell activation and regulation in children with asymptomatic plasmodium falciparum infection","volume":"17","author":"Frimpong","year":"2018","journal-title":"Malaria J"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93434","article-title":"Dichotomous miR expression and immune responses following primary blood-stage malaria","volume":"2","author":"Burel","year":"2017","journal-title":"JCI Insight"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00671","article-title":"CD4 T-cell subsets in malaria: TH1\/TH2 revisited","volume":"5","author":"Perez-Mazliah","year":"2015","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nri1292","article-title":"The many important facets of T-cell repertoire diversity","volume":"4","author":"Nikolich-\u017dugich","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/sj.jid.5700003","article-title":"Immunosurveillance and immunoregulation by \u03b3\u03b4 T cells","volume":"126","author":"Girardi","year":"2006","journal-title":"JJoid"},{"key":"B10","doi-asserted-by":"publisher","first-page":"20140291","DOI":"10.1098\/rstb.2014.0291","article-title":"Estimating T-cell repertoire diversity: limitations of classical estimators and a new approach","volume":"370","author":"Laydon","year":"2015","journal-title":"Philos Trans R Soc London Ser B Biol Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2007.01.019","article-title":"Methods for comparing the diversity of samples of the T cell receptor repertoire","volume":"321","author":"Venturi","year":"2007","journal-title":"J Immunol Methods"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1038\/s41467-017-01925-2","article-title":"T Cell receptor \u03b2-chains display abnormal shortening and repertoire sharing in type 1 diabetes","volume":"8","author":"Gomez-Tourino","year":"2017","journal-title":"Nat Commun"},{"key":"B13","doi-asserted-by":"publisher","first-page":"37543","DOI":"10.1038\/srep37543","article-title":"Autoimmune susceptibility imposed by public TCR\u03b2 chains","volume":"6","author":"Zhao","year":"2016","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00644","article-title":"Dynamic perturbations of the T-cell receptor repertoire in chronic HIV infection and following antiretroviral therapy","volume":"6","author":"Heather","year":"2016","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003646","article-title":"Quantification of HTLV-1 clonality and TCR diversity","volume":"10","author":"Laydon","year":"2014","journal-title":"PloS Comput Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00336","article-title":"High-throughput sequencing-based immune repertoire study during infectious disease","volume":"7","author":"Hou","year":"2016","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-015-0242-3","article-title":"High-throughput sequencing insights into T-cell receptor repertoire diversity in aging","volume":"7","author":"Goronzy","year":"2015","journal-title":"Genome Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048117","article-title":"Limited T cell receptor repertoire diversity in tuberculosis patients correlates with clinical severity","volume":"7","author":"Luo","year":"2012","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.immuni.2017.10.013","article-title":"A T cell receptor locus harbors a malaria-specific immune response gene","volume":"47","author":"Van Braeckel-Budimir","year":"2017","journal-title":"Immunity"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147871","article-title":"A TCR\u03b2 repertoire signature can predict experimental cerebral malaria","volume":"11","author":"Mariotti-Ferrandiz","year":"2016","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.3389\/fimmu.2020.587756","article-title":"A conserved TCR\u03b2 signature dominates a highly polyclonal T-cell expansion during the acute phase of a murine malaria infection","volume":"11","author":"Smith","year":"2020","journal-title":"J Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/11.9.1553","article-title":"T Cell response in malaria pathogenesis: selective increase in T cells carrying the TCR V\u03b28 during experimental cerebral malaria","volume":"11","author":"Boubou","year":"1999","journal-title":"Int Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01345","article-title":"Phenotypic evidence of T cell exhaustion and senescence during symptomatic plasmodium falciparum malaria","volume":"10","author":"Frimpong","year":"2019","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-0716-2189-9_1","article-title":"Identification and enumeration of plasmodium falciparum parasites by light microscopy","volume-title":"Malaria immunology: Targeting the surface of infected erythrocytes","author":"Frimpong","year":"2022"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki065","article-title":"IMGT\u00ae, the international ImMunoGeneTics information system\u00ae","volume":"37","author":"Lefranc","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13073-015-0169-8","article-title":"A bioinformatic framework for immune repertoire diversity profiling enables detection of immunological status","volume":"7","author":"Greiff","year":"2015","journal-title":"Genome Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc.: Ser B (Methodological)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nature22976","article-title":"Et al: Identifying specificity groups in the T cell receptor repertoire","volume":"547","author":"Glanville","year":"2017","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx760","article-title":"VDJdb: a curated database of T-cell receptor sequences with known antigen specificity","volume":"46","author":"Shugay","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.10.6068-6077.2005","article-title":"Functional mimicry of a human immunodeficiency virus type 1 coreceptor by a neutralizing monoclonal antibody","volume":"79","author":"Xiang","year":"2005","journal-title":"J Virol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.885","article-title":"Analysis of the structural correlates for antibody polyreactivity by multiple reassortments of chimeric human immunoglobulin heavy and light chain V segments","volume":"180","author":"Ichiyoshi","year":"1994","journal-title":"J Exp Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-009-0116-7","article-title":"Single domain antibodies: Promising experimental and therapeutic tools in infection and immunity","volume":"198","author":"Wesolowski","year":"2009","journal-title":"Med Microbiol Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.06.026","article-title":"Statistical analysis of CDR3 length distributions for the assessment of T and b cell repertoire biases","volume":"44","author":"Miqueu","year":"2007","journal-title":"Mol Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102661","article-title":"The role of naive T cell precursor frequency and recruitment in dictating immune response magnitude","volume":"188","author":"Jenkins","year":"2012","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41538","article-title":"Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion","volume":"120","author":"La Gruta","year":"2010","journal-title":"J Clin Invest"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-328781","article-title":"Escape from highly effective public CD8+ T-cell clonotypes by HIV","volume":"118","author":"Iglesias","year":"2011","journal-title":"J Am Soc Hematol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83792","article-title":"Public T cell receptors confer high-avidity CD4 responses to HIV controllers","volume":"126","author":"Benati","year":"2016","journal-title":"JTJoci"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3822","article-title":"Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire","volume":"49","author":"Emerson","year":"2017","journal-title":"Nat Genet"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801401","article-title":"Antigen-specific TCR signatures of cytomegalovirus infection","volume":"202","author":"Huth","year":"2019","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01388-06","article-title":"Et al: Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells after early HIV-1 infection","volume":"81","author":"Lichterfeld","year":"2007","journal-title":"J Virol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.03.023","article-title":"T-Cell responses against malaria: Effect of parasite antigen diversity and relevance for vaccine development","volume":"36","author":"Nlinwe","year":"2018","journal-title":"Vaccine"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.323","article-title":"CDR3 length in antigen-specific immune receptors","volume":"179","author":"Rock","year":"1994","journal-title":"J Exp Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/1074-7613(95)90068-3","article-title":"Increased peptide promiscuity provides a rationale for the lack of n regions in the neonatal T cell repertoire","volume":"3","author":"Gavin","year":"1995","journal-title":"Immunity"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13247","article-title":"Altered T cell receptor beta repertoire patterns in pediatric ulcerative colitis","volume":"196","author":"Werner","year":"2018","journal-title":"Clin Exp Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1002\/dmrr.2720","article-title":"T-Cell receptor repertoire variation may be associated with type 2 diabetes mellitus in humans","volume":"32","author":"Frankl","year":"2016","journal-title":"Diabetes\/metabolism Res Rev"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2006.02.007","article-title":"Pathogenic T cells in cerebral malaria","volume":"36","author":"R\u00e9nia","year":"2006","journal-title":"Int J Parasitol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"6148","DOI":"10.4049\/jimmunol.1003955","article-title":"Granzyme b expression by CD8+ T cells is required for the development of experimental cerebral malaria","volume":"186","author":"Haque","year":"2011","journal-title":"J Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/1471-2172-14-35","article-title":"Quantification of total T-cell receptor diversity by flow cytometry and spectratyping","volume":"14","author":"Ciupe","year":"2013","journal-title":"BMC Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1159\/000445656","article-title":"Analysis of the repertoire features of TCR beta chain CDR3 in human by high-throughput sequencing","volume":"39","author":"Hou","year":"2016","journal-title":"Cell Physiol Biochem"},{"key":"B50","doi-asserted-by":"publisher","first-page":"929","DOI":"10.4049\/jimmunol.1402168","article-title":"The V gene repertoires of classical and atypical memory b cells in malaria-susceptible West African children","volume":"194","author":"Zin\u00f6cker","year":"2015","journal-title":"J Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.559255","article-title":"Asymptomatic malaria infection is maintained by a balanced pro- and anti-inflammatory response","volume":"11","author":"Frimpong","year":"2020","journal-title":"Front Microbiol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/cr.2012.1","article-title":"Determinants of public T cell responses","volume":"22","author":"Li","year":"2012","journal-title":"Cell Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608907103","article-title":"Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination","volume":"103","author":"Venturi","year":"2006","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1101\/gr.170753.113","article-title":"T-Cell receptor repertoires share a restricted set of public and abundant CDR3 sequences that are associated with self-related immunity","volume":"24","author":"Madi","year":"2014","journal-title":"Genome Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20032044","article-title":"HIV-Specific cytotoxic T cells from long-term survivors select a unique T cell receptor","volume":"200","author":"Dong","year":"2004","journal-title":"J Exp Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081127","article-title":"Public clonotype usage identifies protective gag-specific CD8+ T cell responses in SIV infection","volume":"206","author":"Price","year":"2009","journal-title":"J Exp Med"},{"key":"B57","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.immuni.2004.10.010","article-title":"T Cell receptor recognition motifs govern immune escape patterns in acute SIV infection","volume":"21","author":"Price","year":"2004","journal-title":"Immunity"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.02.056","article-title":"Et al: System-wide analysis of the T cell response","volume":"14","author":"Covacu","year":"2016","journal-title":"Cell Rep"},{"key":"B59","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nri2260","article-title":"The molecular basis for public T-cell responses","volume":"8","author":"Venturi","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"7039","DOI":"10.4049\/jimmunol.1003309","article-title":"Large TCR diversity of virus-specific CD8 T cells provides the mechanistic basis for massive TCR renewal after antigen exposure","volume":"186","author":"Miconnet","year":"2011","journal-title":"J Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02769","article-title":"Novel strategies for malaria vaccine design","volume":"9","author":"Frimpong","year":"2018","journal-title":"Front Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000021","article-title":"Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: Implications for systemic inflammation and insulin resistance","volume":"185","author":"Yang","year":"2010","journal-title":"JTJoI"},{"key":"B63","doi-asserted-by":"publisher","first-page":"88","DOI":"10.4269\/ajtmh.2007.77.88","article-title":"Hygiene: Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia and prospects for combining control","volume":"77","author":"Brooker","year":"2007","journal-title":"JTAjotm"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-018-5965-9","article-title":"Co-Infection: the outcome of plasmodium infection differs according to the time of pre-existing helminth infection","volume":"117","author":"Salazar-Casta\u00f1\u00f3n","year":"2018","journal-title":"JPr"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.971392\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T01:48:50Z","timestamp":1665625730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.971392\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":64,"alternative-id":["10.3389\/fimmu.2022.971392"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.971392","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,13]]},"article-number":"971392"}}