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While CD8\n +<\/jats:sup>\n Trm populations in these compartments differ in longevity and developmental requirements, it remains unclear whether they share clonotypes, indicating a common origin, or are seeded by distinct T\u2010cell clones. Using a mouse model of influenza virus infection, we investigated the T\u2010cell receptor (TCR) composition of CD8\n +<\/jats:sup>\n Trm specific for two immunodominant influenza\u2010specific CD8\n +<\/jats:sup>\n T\u2010cell epitopes, derived from the nucleoprotein (NP\n 366\u2010374<\/jats:sub>\n ) and polymerase acidic protein (PA\n 224\u2010233<\/jats:sub>\n ). TCR\u03b1\u03b2 repertoire analysis of NP\n 366\u2010374<\/jats:sub>\n \u2010specific CD8\n +<\/jats:sup>\n T\u00a0cells from the nasal mucosa, lung and spleen revealed substantial clonal overlap across resident and circulating subsets, consistent with derivation from a shared precursor pool. In contrast, PA\n 224\u2010233<\/jats:sub>\n \u2010specific responses showed minimal clonal sharing across tissues and subsets, reflecting a more diverse and private repertoire. Thus, nasal and lung CD8\n +<\/jats:sup>\n Trm can arise from either shared or distinct clonotypes, with their profiles shaped primarily by the antigen specificity rather than tissue location. This allows barrier tissues to be seeded by both highly conserved, public NP\n 366\u2013374<\/jats:sub>\n \u2010specific CD8\n +<\/jats:sup>\n TCRs and a more diverse, private PA\n 224\u2013233<\/jats:sub>\n \u2010specific repertoire, together forming an optimal pool capable of providing broadly cross\u2010reactive T\u2010cell immunity and limiting viral escape.\n <\/jats:p>","DOI":"10.1111\/imcb.70098","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:53:06Z","timestamp":1772963586000},"page":"358-367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antigen specificity, not tissue compartment, determines clonal sharing among respiratory tract\n CD8<\/scp>\n +<\/sup>\n resident memory T\u00a0cells"],"prefix":"10.1111","volume":"104","author":[{"given":"Thi H O","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayley A","family":"McQuilten","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Pizzolla","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sneha","family":"Sant","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim L","family":"Harland","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Braverman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Kedzierska","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC 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