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T Cell Receptor Repertoire in Polymyositis : Clonal Expansion of Autoaggressive CD 8 + T Cells

In polymyositis (PM), CD8 + T cell receptor (TCR) all3 + cells invade and destroy major histocompatibility complex class I-positive muscle fibers. We combined polymerase chain reaction (PCR) and double-fluorescence immunocytochemistry to analyze the T cell receptor (TCR) repertoire expressed in muscle of PM patients. In patient 1, inverse PCR revealed a preferential usage of TCR Vot33.1, V313.1, and V35.1. Six of six TCR Vot33.1 § clones and five of seven V/313.1 + clones had identical nucleotide sequences. In contrast, the VB5.1 + TCRs were more heterogeneous. Similar results were obtained with an independent PCR method using primers specific for TCR Vot33, V/313, or VBS. No TCR sequences could be amplified from noninflammatory control muscle. Furthermore, none of the TCR sequences found in PM muscle could be detected in blood from the same patient or from a normal control subject. Immunohistochemistry confirmed that V135.1 and Vr were overrepresented in the muscle lesions of this patient. 32% of all CD8 + T cells were V/313.1 +, and 16% were V/35.1 +. However, "~60% of the CD8 § T cells that invaded muscle fibers were V/313.1 +, whereas 10% were V/35.1 +. In patient 2, 50% of the T cells were V/35.1+, and as in patient 1, these T cells were mainly located in interstitial areas. In patient 3, >75% of the autoinvasive T cells stained with an anti-V~3 mAb. Sequence analysis of 15 PCR clones amplified with a V~3-specific primer showed that 9 (60%) sequences were identical. The results suggest that (a) a strikingly limited TCR repertoire is expressed in PM muscle; (b) there is a dissociation between the TCR usage of autoinvasive and interstitial T ceils; and (c) the autoinvasive T cells are clonally expanded.