Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology.
Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T (IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the beta-chain (V beta 7) in these IIT cells in association with unselected V alpha-chain segments; extensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.
Conrad
B
B
Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, Pennsylvania.
Weidmann
E
E
Trucco
G
G
Rudert
W A
WA
Behboo
R
R
Ricordi
C
C
Rodriquez-Rilo
H
H
Finegold
D
D
Trucco
M
M
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001345:Autoradiography; D002454:Cell Differentiation; D002462:Cell Membrane / Q000276:immunology; D002648:Child; D002999:Clone Cells; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D001324:Autoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens