Restricted junctional diversity of T cell receptor delta gene rearrangements expressed in systemic lupus erythematosus (SLE) patients.
SLE is an autoimmune connective tissue disorder affecting multiple organs, in which T cells may play a central role. This study investigated T cell receptor (TCR) gamma/delta repertoire expression in peripheral blood mononuclear cells (PBMC) of SLE patients and healthy individuals using variable (V) gene family-specific polymerase chain reaction (PCR) amplification of TCR cDNA. The expressed V gamma repertoires were diverse in SLE and control PBMC, although V gamma IV gene rearrangements were barely detectable or not expressed in some patients. In contrast, delta chain expression was limited in all SLE patients, with delta transcripts rearranged primarily to the V delta 1 and V delta 2 genes, as opposed to control PBMC, in which all six V delta genes were detected. To assess the clonality of TCR populations, cDNA clones containing rearranged V delta 1, V delta 2 and V gamma 9 transcripts were sequenced from PBMC of both patients and controls. For controls, delta chain junctional region sequences showed extensive molecular heterogeneity, since virtually all 34 V delta 1 and 32 V delta 2 cDNA clones analysed were unique. A few V gamma 9 cDNA clones (3/21) had the same junctional region sequence motif (EVQEL) encoded largely by the V gamma 9 and joining (J) gamma P gene segments. Identical V gamma 9 junctional sequences were found in SLE patients that did not contain the EVQEL motif present in normal peripheral blood gamma/delta lymphocytes. Moreover, the predominant V delta 1-J delta -constant (C) delta and V delta 2-J delta-C delta gene rearrangements expressed in SLE PBMC showed restricted junctional diversity, but the oligoclonal delta transcripts were different in each patient. These findings suggest in vivo oligoclonal expansion of gamma/delta T cells in the periphery of SLE patients in response to a limited number of nominal ligands. Whether gamma/delta T cells contribute to the development of systemic autoimmunity remains to be investigated.
Olive
C
C
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra.
Gatenby
P A
PA
Serjeantson
S W
SW
D000328:Adult; D000368:Aged; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D015345:Oligonucleotide Probes; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004247:DNA