The alpha beta T-cell receptor repertoire in inclusion body myositis: diverse patterns of gene expression by muscle-infiltrating lymphocytes.
Inclusion body myositis (IBM) is one member of a group of disorders known as idiopathic inflammatory myopathies (IIM) in which autoreactive T cells directed against muscle are thought to play a primary role in disease pathogenesis. We have utilized the polymerase chain reaction to determine the pattern of alpha beta T-cell receptor (TCR) variable (V) gene expression in muscle biopsies from 13 IBM patients. In the majority of biopsies, we detected oligoclonal patterns of TCR V gene expression by muscle-infiltrating lymphocytes; an average of six out of the 22 TCR V alpha gene families surveyed and seven out of 24 TCR V beta gene families surveyed were detected per biopsy. While no TCR V alpha gene families were over-represented in our survey, TCR V beta 3 and V beta 6 gene usage was a prominent feature of IBM muscle biopsies. TCR gene expression was characterized further by analysing the junctional sequence composition of both V beta 3 and V beta 6 clones from muscle biopsies of the IBM patients. A large number of structurally diverse V beta 3 and V beta 6 clonotypes were identified from these patients demonstrating a polyclonal pattern of T cell infiltration. These data, while describing prominent TCR V beta 3 and V beta 6 gene detection, do not suggest that a common antigen-driven T-cell response promotes chronic inflammation in muscle of IBM patients.
O'Hanlon
T P
TP
Laboratory of Molecular Immunology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Dalakas
M C
MC
Plotz
P H
PH
Miller
F W
FW
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D015870:Gene Expression; D006801:Humans; D002479:Inclusion Bodies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009220:Myositis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D017931:DNA Primers; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta