CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups.
We examined CD4+ T cell TCRBV-CDR3 transcripts from 19 lupus patients and 16 controls to test the hypothesis that CD4+ TCRBV-CDR3 expression in SLE differs from normals. Within the disease group we also performed exploratory analyses to determine the association between risk of oligoclonality and HLA-DRB specificities and the duration of the CDR3 patterns. Oligoclonal patterns consistent with CDR3 restriction were three times more likely in SLE than in controls (OR = 3.7). TCRBV1, BV4, BV5.1, BV7, BV9, BV18 and BV22 gene segment CDR3 patterns of oligoclonality were seen exclusively among lupus patients. HLA-DRB3 increased the risk of oligoclonal expression in SLE. In four patients studied over time, the pattern of TCRBV-CDR3 expression was stable in a second sample obtained 6-14 months later. The increased frequency of CD4+ T cell TCRBV-CDR3 oligoclonal expression in SLE when compared to controls and the persistence of these patterns are consistent with an expanded pool of autoreactive CD4 T cells in SLE which recognize peptides derived from autoantigens. The association of HLA-DRB3 genes with increased risk of CDR3 oligoclonality among the SLE subjects is compatible with the hypothesis that molecules encoded by HLA-DRB3 may facilitate autoantigen recognition by CD4 T cells.
Center for Blood Research, Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
P A
PA
Fraser
L Y
LY
Lu
K
K
DeCeulaer
P H
PH
Schur
D
D
Fici
Z
Z
Awdeh
W Z
WZ
Ding
E
E
Levitan
R
R
Lew
G
G
Uko
C
C
Gonzalez
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D044383:Black People; D017252:CD3 Complex / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D004247:DNA / Q000276:immunology; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D059847:HLA-DRB5 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology* / Q000276:immunology*; D008875:Middle Aged; D015995:Prevalence; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D044465:White People
D000974:Antibodies, Antinuclear; D017252:CD3 Complex; D017931:DNA Primers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D059847:HLA-DRB5 Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA