Autoreactive T cells identified in patients with anti-Jo1+ antisynthetase syndrome recognise a new epitope on histidyl t-RNA synthetase
Authors' conclusion
Autoreactive T-cells targeting a new HisRS epitope were identified indicating T cell reactivity to diverse epitopes of the HisRS protein in patients with anti-Jo1 autoantibodies. Furthermore, we demonstrated the TCR repertoire of autoreactive HisRS+CD4+T cells in patients. Persistence of these T-cells and specific clones may be contributing to disease.
Study context
- Population
- Patients with anti-Jo1+ antisynthetase syndrome (ASyS) carrying HLA-DRB1*03:01HLA-DRB1*03:01 positive
- Participants
- 12 patients
- Outcome
- Identification of new HisRS T cell epitopes, presence of autoreactive HisRS+CD4+T cells and their TCR repertoire
Methodological detailsin vitro binding assays, HLA-class II tetramer detection, single T-cell receptor (TCR) sequencing, Peptides from HisRS N-terminal region with appropriate major histocompatibility complex (MHC) anchor residues selected for in vitro binding assays; HisRS41-55 with highest HLA-DRB1*03:01 binding affinity selected for tetramer studies
- In vitro binding assays
- HLA-class II tetramer detection
- Single TCR sequencing
- Peptides from HisRS N-terminal region with appropriate MHC anchor residues selected for in vitro binding assays; HisRS41-55 with highest HLA-DRB1*03:01 binding affinity selected for tetramer studies
Main finding
As reported in the abstract
Autoreactive HisRS+CD4+T cells detected in peripheral blood mononuclear cells (PBMCs) of patients
n = 6/12
HisRS+CD4+T cells persisted after treatment
2 patients
P2 and P4
Identical T cell clones detected between initial and follow-up time points
2 clones in 1 patient
P2
Further findings
Persistence of HisRS+CD4+T cells after treatment · follow-up
- HisRS+CD4+T cells persisted after treatment
- 2 patients (P2 and P4)
- Identical T cell clones between initial and follow-up time points
- 2 clones in 1 patient (P2)
Original publication
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