T cell receptor alpha-chain and beta-chain junctional region homology in clonal CD3+,CD8+ T lymphocyte expansions in Felty's syndrome

Objective. Up to 42% of patients with Felty's syndrome (FS) have peripheral blood expansions of CD3+,CD8+ large granular lymphocytes (LGLs), The aim of this study was to determine whether the T cell receptor (TCR) alpha- and beta-chain sequences of these expansions from different patients have features in common that would support the hypothesis of an antigen-driven process. Methods. Extraction of RNA from peripheral blood lymphocytes followed by synthesis of complementary DNA, inverse polymerase chain reaction (PCR) with TCR-specific primers, bacteriophage transformation, and sequencing of PCR products. Results. Structural analysis of TCR beta-chain usage in such patients demonstrated a junctional region motif comprising the amino acids -LG- or -RG- in 7 of 14 clonal sequences and the motif -GXG- in 8 of 14, A biased alpha-chain junctional region usage of a hydrophobic and/or basic amino acid at position 2 was seen in 5 of 8 expanded sequences, These features differed significantly from control sequences. Conclusion. Given current models of TCR-peptide-major histocompatibility complex interaction, these observations are consistent with an antigen-driven, rather than a superantigen-driven, process in at least a subgroup of patients with FS.