T cell receptor α‐chain and β‐chain junctional region homology in clonal CD3+, CD8+ T lymphocyte expansions in Felty'S syndrome

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Abstract
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) α‐ and β‐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 β‐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 α‐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.