PMID- 37886513
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240508
DP  - 2023 Oct 20
TI  - Self-reactive germline-like TCR alpha chains shared between blood and pancreas.
LID - rs.3.rs-3446917 [pii]
LID - 10.21203/rs.3.rs-3446917/v1 [doi]
AB  - Human islet antigen reactive CD4 + memory T cells (IAR T cells) from peripheral 
      blood have been studied extensively for their role in the pathogenesis of 
      autoimmune type 1 diabetes (T1D). However, IAR T cells are rare, and it remains 
      poorly understood how they affect T1D progression in the pancreas. Using single 
      cell RNA-sequencing coupled with a multiplexed activation induced marker (AIM) 
      enrichment assay, we identified paired TCR alpha/beta (TRA/TRB) T cell receptors 
      (TCRs) in IAR T cells from the blood of healthy, at-risk, new onset, and 
      established T1D donors. Using TCR sequences as barcodes, we measured infiltration 
      of IAR T cells from blood into pancreas of organ donors with and without T1D. We 
      detected extensive TCR sharing between IAR T cells from peripheral blood and 
      pancreatic infiltrating T cells (PIT), with perfectly matched or single 
      mismatched TRA junctions and J gene regions, comprising ~ 34% of unique IAR TCRs. 
      PIT-matching IAR T cells had public TRA chains that showed increased use of 
      germline-encoded residues in epitope engagement and a propensity for 
      cross-reactivity. The link with T cells in the pancreas implicates autoreactive 
      IAR T cells with shared TRA junctions and increased levels in blood with the 
      prediabetic and new onset phases of T1D progression.
FAU - Linsley, Peter
AU  - Linsley P
AUID- ORCID: 0000-0002-8960-4307
AD  - Benaroya Research Institute at Virginia Mason.
FAU - Nakayama, Maki
AU  - Nakayama M
AD  - Barbara Davis Center for Childhood Diabetes.
FAU - Balmas, Elisa
AU  - Balmas E
AD  - Benaroya Research Institute.
FAU - Chen, Janice
AU  - Chen J
AD  - Benaroya Research Institute.
FAU - Pour, Fariba
AU  - Pour F
AD  - Benaroya Research Institute.
FAU - Bansal, Shubham
AU  - Bansal S
AD  - Benaroya Research Institute.
FAU - Serti, Elisavet
AU  - Serti E
AUID- ORCID: 0000-0003-4129-0254
AD  - The Henry Jackson Foundation.
FAU - Speake, Cate
AU  - Speake C
AUID- ORCID: 0000-0003-1480-4272
AD  - Benaroya Research Institute.
FAU - Pugliese, Alberto
AU  - Pugliese A
AD  - City of Hope.
FAU - Cerosaletti, Karen
AU  - Cerosaletti K
AUID- ORCID: 0000-0002-7403-6239
AD  - Benaroya Research Institute, Seattle, WA.
LA  - eng
GR  - U24 DK098085/DK/NIDDK NIH HHS/United States
GR  - UM1 AI109565/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20231020
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
PMC - PMC10602137
EDAT- 2023/10/27 06:42
MHDA- 2023/10/27 06:43
PMCR- 2023/10/26
CRDT- 2023/10/27 04:43
PHST- 2023/10/27 06:42 [pubmed]
PHST- 2023/10/27 06:43 [medline]
PHST- 2023/10/27 04:43 [entrez]
PHST- 2023/10/26 00:00 [pmc-release]
AID - rs.3.rs-3446917 [pii]
AID - 10.21203/rs.3.rs-3446917/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Oct 20:rs.3.rs-3446917. doi: 10.21203/rs.3.rs-3446917/v1.