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.


CONCLUSIONS
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.
Bowman
S J
SJ
United Medical and Dental Schools, Guy's Hospital, London, UK.
Hall
M A
MA
Panayi
G S
GS
Lanchbury
J S
JS
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D017931:DNA Primers / Q000737:chemistry; D005258:Felty Syndrome / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D018089:Superantigens / Q000276:immunology
D017252:CD3 Complex; D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens