Stephanie J. Hanna1  · Rachel H. Bonami2,3,4,5  · Brian Corrie6,7  · Monica Westley8  · Amanda L. Posgai9  · Eline T. Luning Prak10  · Felix Breden6,7  · Aaron W. Michels11  · Todd M. Brusko9,12,13  · Type 1 Diabetes AIRR Consortium

Received: 26 May 2024 / Accepted: 19 August 2024 / Published online: 29 October 2024

© The Author(s) 2024

Extended author information available on the last page of the article

Abstract

Human molecular genetics has brought incredible insights into the variants that confer risk for the development of tissuespecific 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.

Keywords AIRR · AIRR Data Commons · Autoantibodies · B cell receptors · FAIR data · Next-generation sequencing · Single-cell RNA-seq · T cell receptors · Type 1 diabetes

Abbreviations

AAb  Autoantibody/autoantibodies

ADC  AIRR Data Commons

AIM  Activation-induced marker

AIRR  Adaptive Immune Receptor Repertoire

AIRR-seq  AIRR sequencing

BCR  B cell receptor

CDR3  Complementarity determining region 3

FAIR  Findable, Accessible, Interoperable, Reusable

GEO  Gene Expression Omnibus

HPAP  Human Pancreas Analysis Program

IEDB  Immune Epitope Database

MiAIRR  Minimal information about AIRR

ML  Machine learning

pLN  Pancreatic lymph node(s)

SARS-CoV-2  Severe acute respiratory syndrome coronavirus 2

scRNA-seq  Single-cell RNA-seq

SRA  Sequence Read Archive 

T1D TCR/BCR Repository The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository

TCR  T cell receptor

TCRβ  T cell receptor β chain

Tfh   T follicular helper

Treg  Regulatory T cell(s)

VDJ  Variable, diversity and joining gene segments

Stephanie J. Hanna and Rachel H. Bonami contributed equally to this work. Aaron W. Michels and Todd M. Brusko contributed equally as joint senior authors.

Members of the Type 1 Diabetes AIRR Consortium are listed in the  Acknowledgements.