The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository in the AIRR Data Commons: a practical guide for access, use and contributions through the Type 1 Diabetes AIRR Consortium

• Published in: Diabetologia 2025, Vol.68 (1), p.186-202
• Main Authors: Hanna, Stephanie J., Bonami, Rachel H., Corrie, Brian, Westley, Monica, Posgai, Amanda L., Luning Prak, Eline T., Breden, Felix, Michels, Aaron W., Brusko, Todd M.
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Autoimmunity; B-cell receptor; Beta cells; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Extended; Extended Article; Genes; Human Physiology; Humans; Internal Medicine; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Metabolic Diseases; Phenotypes; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - metabolism; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Single-nucleotide polymorphism; T cell receptors
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-024-06298-y

Human molecular genetics has brought incredible insights into the variants that confer risk for the development of tissue-specific autoimmune diseases, including type 1 diabetes. The hallmark cell-mediated immune destruction that is characteristic of type 1 diabetes is closely linked with risk conferred by the HLA class II gene locus, in combination with a broad array of additional candidate genes influencing islet-resident beta cells within the pancreas, as well as function, phenotype and trafficking of immune cells to tissues. In addition to the well-studied germline SNP variants, there are critical contributions conferred by T cell receptor (TCR) and B cell receptor (BCR) genes that undergo somatic recombination to yield the Adaptive Immune Receptor Repertoire (AIRR) responsible for autoimmunity in type 1 diabetes. We therefore created the T1D TCR/BCR Repository (The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository) to study these highly variable and dynamic gene rearrangements. In addition to processed TCR and BCR sequences, the T1D TCR/BCR Repository includes detailed metadata (e.g. participant demographics, disease-associated parameters and tissue type). We introduce the Type 1 Diabetes AIRR Consortium goals and outline methods to use and deposit data to this comprehensive repository. Our ultimate goal is to facilitate research community access to rich, carefully annotated immune AIRR datasets to enable new scientific inquiry and insight into the natural history and pathogenesis of type 1 diabetes. Graphical Abstract