Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. Restricted V alpha/beta rearrangements may indicate antigen-driven selection.
Polymyositis is an inflammatory myopathy characterized by mononuclear cell infiltration of muscle tissue. Myocytotoxic T lymphocytes have been recognized in the infiltrates, but the muscle antigen, target of the immune attack, has not been identified. Molecular characterization of the variable regions of T cell receptors (TCRs) on the infiltrating lymphocytes can be expected to provide insights into the pathogenic process. The V alpha/beta TCR repertoire was investigated by RNA-PCR in muscle biopsies from 15 polymyositis patients and 16 controls (6 Duchenne muscular dystrophy and 10 with no inflammatory or dystrophic myopathy). A variety of rearranged variable TCR genes was found in polymyositis, V alpha 1, V alpha 5, V beta 1, and V beta 15 being the most common (present in 60-100% of patients). In Duchenne muscular dystrophy patients TCR V alpha or beta rearrangements were found although no restriction was observed; no rearrangements were found in muscles from the other controls. Sequence analysis revealed the presence of the J beta 2.1 region in 90% of the V beta 15 clones studied, no random N additions in the diversity region, and a common motif within the CDR3 region. These results suggest that selection of muscle-infiltrating T lymphocytes is antigen driven in polymyositis.
Mantegazza
R
R
Department of Neuromuscular Diseases, C. Besta National Neurological Institute, Milan, Italy.
Andreetta
F
F
Bernasconi
P
P
Baggi
F
F
Oksenberg
J R
JR
Simoncini
O
O
Mora
M
M
Cornelio
F
F
Steinman
L
L
D000595:Amino Acid Sequence; D001483:Base Sequence; D002465:Cell Movement; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009132:Muscles / Q000276:immunology*; D009136:Muscular Dystrophies / Q000276:immunology; D017285:Polymyositis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta