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

Mariapaola Marino, Maria Teresa Maiuri, Gabriele Di Sante, Flavia Scuderi, Francesca La Carpia, Nikolaos Trakas, Carlo Provenzano, Paraskevi Zisimopoulou, Francesco Ria, Socrates J. Tzartos, Amelia Evoli Stampanoni-B, Emanuela Bartoccioni

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

22 Citazioni (Scopus)


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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaJournal of Autoimmunity
Stato di pubblicazionePubblicato - 2014


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


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