Conserved T cell receptor alpha-chain induces insulin autoantibodies.
A fundamental question is what are the molecular determinants that lead to spontaneous preferential targeting of specific autoantigens in autoimmune diseases, such as the insulin B:9-23 peptide sequence in type 1 diabetes. Anti-insulin B:9-23 T cell clones isolated from prediabetic NOD islets have a conserved Valpha-segment/Jalpha-segment, but no conservation of the alpha-chain N region and no conservation of the Vbeta-chain. Here, we show that the conserved T cell receptor alpha-chain generates insulin autoantibodies when transgenically or retrogenically introduced into mice without its corresponding Vbeta. We suggest that a major part of the mystery as to why islet autoimmunity develops relates to recognition of a primary insulin peptide by a conserved alpha chain T cell receptor.
Kobayashi
Masakazu
M
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
Jasinski
Jean
J
Liu
Edwin
E
Li
Marcella
M
Miao
Dongmei
D
Zhang
Li
L
Yu
Liping
L
Nakayama
Maki
M
Eisenbarth
George S
GS
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001483:Base Sequence; D002999:Clone Cells / Q000276:immunology; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D007328:Insulin / Q000276:immunology*; D007330:Insulin Antibodies / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D017931:DNA Primers; D007328:Insulin; D007330:Insulin Antibodies; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma