Molecular analysis of T cell receptor beta variability in a patient with orofacial granulomatosis.

Abstract

Orofacial granulomatosis (OFG) is a rare chronic inflammatory disorder of unknown causation and is characterised histologically by non-caseating granulomas and aggregates of small lymphocytes. The molecular nature of these T cells is, however, unclear. To determine the T cell receptor (TCR) V beta gene usage of the T cell infiltrate associated with the primary lesions in a patient with OFG. A molecular method involving reverse transcriptase (RT)-polymerase chain reaction (PCR), DNA cloning, single strand conformation polymorphism (SSCP), length analysis, and nucleotide sequencing was used. Compared with peripheral blood lymphocytes from the same patient, notably restricted TCRV beta gene usage was observed in the T cell infiltrate. Only three of the 24 major TCRV beta gene families were represented in the repertoire. There was preferential usage of the V beta 6 gene. In addition, more than 20% of the V beta 6 TCR transcripts exhibited an identical unique V-D-J junctional sequence, suggesting a local antigen driven V beta 6 T cell clonal expansion in vivo, a phenomenon not observed in normal oral mucosa. The TCRV beta repertoire of T cells associated with OFG is restricted. It is also associated with a local T cell clonal expansion. The results, therefore, provide a new perspective on the immunopathology of OFG.