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Here, we investigated T cell receptor (TCR) clonotypic signatures within these universal A2\/PB1413+CD8+ T cell pools, compared with immunodominant influenza A\u2013specific M158+CD8+ T cells and codominant influenza B\u2013specific A2\/HA543+CD8+ memory T cells. Using single-cell reverse transcriptase polymerase chain reaction and RNA sequencing methodologies, we defined TCR\u03b1\u03b2 repertoire composition and diversity. Our study shows that CD8+ T cells responding to these 3 epitopes differ in magnitude and TCR\u03b1\u03b2 repertoires in terms of gene usage and sharing, underpinned by specific TCR and structural features for each pMHC-I specificity. Our data demonstrated that the A2\/PB1413+CD8+ TCR\u03b1\u03b2 repertoire encompassed diverse gene segment usage within both TCR\u03b1 and TCR\u03b2 chains. These were, however, greatly variable across HLA-A2*02:01\u2013expressing individuals and lacked any shared features within TRAV, TRBV, TRBJ, and TRAJ gene segments. This A2\/PB1413+CD8+ TCR\u03b1\u03b2 diversity stemmed from the low probability of recombination attributed to a large number of N-insertions in the TCR\u03b2 chain. PB1413+CD8+ T cells also displayed remarkable plasticity in recognition of the A2\/PB1413 epitope depicted by versatile CD8+ T cell recognition patterns of the universal A2\/PB1413 epitope across HLA-A*02:01\u2013expressing individuals. Conversely, TCR\u03b1\u03b2 repertoires within A2\/BHA543+CD8+ and M158+CD8+ T cells displayed common TRAV, TRBV, TRBJ, and TRAJ gene segments, shared across HLA-A*02:01\u2013expressing individuals and recognizing key residues within A2\/BHA543 and A2\/M158 epitopes. Overall, our data showed a great level of TCR\u03b1\u03b2 gene usage diversity within universal A2\/PB1413+CD8+ T cells, indicating that the TCR\u03b1\u03b2 clonal plasticity defines universal immunity toward human influenza viruses.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag270","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:40:41Z","timestamp":1792168841000},"source":"Crossref","is-referenced-by-count":0,"title":["TCR\u03b1\u03b2 repertoire plasticity defines universal CD8+ T cell responses directed at influenza-specific HLA-A*02:01-PB1413\u2013421 epitope"],"prefix":"10.1093","volume":"215","author":[{"given":"Marios","family":"Koutsakos","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne and Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy 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Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0649-5089","authenticated-orcid":false,"given":"Louise C","family":"Rowntree","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne and Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma Kaitlynn","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Host-Microbe Interactions, St. Jude Children\u2019s Research Hospital , Memphis, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-8356","authenticated-orcid":false,"given":"Steven Y C","family":"Tong","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Service, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]},{"name":"Department of Infectious Diseases, University of Melbourne and Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3152-116X","authenticated-orcid":false,"given":"Allen C","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University , Melbourne, Victoria,","place":["Australia"]},{"name":"Monash Infectious Diseases, Monash Health and School of Clinical Sciences, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom C","family":"Kotsimbos","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The Alfred Hospital , Melbourne, Victoria,","place":["Australia"]},{"name":"Department of Medicine, Central Clinical School, The Alfred Hospital, Monash University , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Luciani","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, UNSW Sydney , Sydney, New South Wales,","place":["Australia"]},{"name":"The Westmead Institute of Medical Research, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Rossjohn","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Gras","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery 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