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DOCK8 deficiency leads to combined immunodeficiency characterized by susceptibility to infections, autoimmunity, and a severe Th2\u2010type immune response. While dysfunction in various T cell subsets has been implicated in these phenotypes, a comprehensive analysis of the T\u2010cell receptor (TCR) repertoire in these patients has not yet been documented. This study investigates the \u03b1\u03b2 TCR repertoire in DOCK8\u2010deficient patients to identify features related to disease pathogenesis and explore the potential role of TCR repertoire alterations in disease development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared immune repertoire profiles determined by high\u2010throughput TCR sequencing of circulating CD4+ and CD8+ T cells from patients with DOCK8 deficiency (<jats:italic>n<\/jats:italic>\u2009=\u200910) to healthy controls (<jats:italic>n<\/jats:italic>\u2009=\u20097) and patients with ataxia\u2010telangiectasia (AT) (<jats:italic>n<\/jats:italic>\u2009=\u20095).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Different diversity analyses revealed a restricted TRA and TRB repertoire in both CD4+ and CD8+ T cells from DOCK8\u2010deficient patients, with the restriction being more pronounced in CD8+ T cells. Skewed usage of individual variable (V) and joining (J) genes and potentially self\u2010reactive CD8+ T cell clones, as determined by hydrophobicity and cysteine indices, were identified in DOCK8\u2010deficient patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study represents the most comprehensive immune repertoire analysis in DOCK8 deficiency. The identification of a significantly restricted \u03b1\u03b2 TCR repertoire, along with the detection of potentially autoreactive clones, highlights the crucial role of immune repertoire profiling in elucidating the pathogenesis of DOCK8 deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16580","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T09:25:33Z","timestamp":1747387533000},"page":"2519-2530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comprehensive \u03b1\u03b2 T\u2010Cell Receptor Repertoire Analysis Reveals a Unique CD8+ TCR Landscape in DOCK8\u2010Deficient Patients"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-5655","authenticated-orcid":false,"given":"Ceren","family":"Bozkurt","sequence":"first","affiliation":[{"name":"Can Sucak Research Laboratory for Translational Immunology Hacettepe University  Ankara 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