Comprehensive αβ T‐Cell Receptor Repertoire Analysis Reveals a Unique CD8+ TCR Landscape in DOCK8‐Deficient Patients
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) is a guanine nucleotide exchange factor highly expressed in, and critical for, the function of various innate and adaptive immune cells. DOCK8 deficiency leads to combined immunodeficiency characterized by susceptibility to infections, autoimmunity, and a severe Th2-type immune response. While dysfunction in various T cell subsets has been implicated in these phenotypes, a comprehensive analysis of the T-cell receptor (TCR) repertoire in these patients has not yet been documented. This study investigates the αβ TCR repertoire in DOCK8-deficient patients to identify features related to disease pathogenesis and explore the potential role of TCR repertoire alterations in disease development. METHODS: We compared immune repertoire profiles determined by high-throughput TCR sequencing of circulating CD4+ and CD8+ T cells from patients with DOCK8 deficiency (n = 10) to healthy controls (n = 7) and patients with ataxia-telangiectasia (AT) (n = 5). RESULTS: Different diversity analyses revealed a restricted TRA and TRB repertoire in both CD4+ and CD8+ T cells from DOCK8-deficient patients, with the restriction being more pronounced in CD8+ T cells. Skewed usage of individual variable (V) and joining (J) genes and potentially self-reactive CD8+ T cell clones, as determined by hydrophobicity and cysteine indices, were identified in DOCK8-deficient patients. CONCLUSION: Our study represents the most comprehensive immune repertoire analysis in DOCK8 deficiency. The identification of a significantly restricted αβ 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.
Source: Allergy
DOI: 10.1111/all.16580
Authors: Ceren Bozkurt, Gökhan Cildir, Umran Aba, Rahmi Kutay Erdogan, Nicholas I Warnock, Chung Hoow Kok, Asena Pinar Sefer, Sule Haskologlu, Sidem Didar Tekeoglu, Gülşah Merve Kılınç, Canberk Ipsir, Tugba Arikoglu, Aylin Kont Ozhan, Saliha Esenboga, Ahmet Özen, Elif Karakoç‐Aydiner, Sevgi Bilgiç Eltan, Çigdem Aydogmus, Candan Islamoglu, Kübra Baskın, Betul Karaatmaca, Ayse Metin, Deniz Çagdaş, Figen Dogu, Aydan Ikinciogullari, Safa Baris, Baran Erman
Institutions: Hacettepe University, South Australia Pathology, University of South Australia, Centre for Cancer Biology, The University of Adelaide, Recep Tayyip Erdoğan University, Ankara University, Mersin Üniversitesi, Marmara University, Sağlık Bilimleri Üniversitesi, İstanbul Başakşehir Çam ve Sakura Şehir Hastanesi, Gazi University, Ankara Bilkent City Hospital
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,300
Awards: G4252511277, G962594629
OpenAlex ID: W4410285803