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J Autoimmun. 2014 Aug;52:113-21. doi: 10.1016/j.jaut.2013.12.007. Epub 2014 Jan 4.

T cell repertoire in DQ5-positive MuSK-positive myasthenia gravis patients.

Author information

1
General Pathology Institute, Università Cattolica del Sacro Cuore, Largo F. Vito, 1, 00168 Rome, Italy.
2
Department of Biochemistry, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, 11521 Athens, Greece.
3
Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo F. Vito, 1, 00168 Rome, Italy. Electronic address: a.evoli@rm.unicatt.it.
4
General Pathology Institute, Università Cattolica del Sacro Cuore, Largo F. Vito, 1, 00168 Rome, Italy. Electronic address: ebartoc@rm.unicatt.it.

Abstract

Myasthenia gravis (MG) is a prototypical antibody-mediated disease characterized by muscle weakness and fatigability. Serum antibodies to the acetylcholine receptor and muscle-specific tyrosine kinase receptor (MuSK) are found in about 85% and 8% of patients respectively. We have previously shown that more than 70% of MG patients with MuSK antibodies share the HLA DQ5 allele. The aim of the present study was to analyze the T cell receptor (TCR) repertoire specific for recombinant human MuSK protein. We used the CDR3 TRBV-TRBJ spectratyping (immunoscope) to analyze the T cell response to MuSK from 13 DQ5+ MuSK-MG patients and from 7 controls (six DQ5+ MuSK negative subjects and one DQ5- DQ3+ MuSK positive patient). DQ5+ MuSK-MG patients but not controls used a restricted set of TCR VJ rearrangements in response to MuSK stimulation. One semiprivate (TRBV29-TRBJ2.5) rearrangement was found in 5/13 patients, while 4 other semiprivate (one in TRBV28-TRBJ2.1 and in TRBV3-TRBJ1.2, and two in TRBV28-TRBJ1.2) rearrangements were differently shared by 4/13 patients each and were absent in controls. When we sequenced the TRBV29-TRBJ2.5 rearrangement, we obtained 26 different sequences of the expected 130 bp length from 117 samples of the 5 positive patients: two common motifs GXGQET/TEHQET were shared in 4 patients as semiprivate motifs. Thus, the MuSK-specific T-cell response appears to be restricted in DQ5+ MuSK-MG patients, with a semiprivate repertoire including a common motif of TRBV29. This oligoclonal restriction of T cells will allow the identification of immunodominant epitopes in the antigen, providing therefore new tools for diagnosis and targeted therapy.

KEYWORDS:

CDR3; Immunoscope; MHC; Repertoire; Spectratyping; T cell receptor

PMID:
24397960
DOI:
10.1016/j.jaut.2013.12.007
[Indexed for MEDLINE]

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