Aspartate at position 57 of nonobese diabetic I-Ag7 beta-chain diminishes the spontaneous incidence of insulin-dependent diabetes mellitus.
MHC class II genes have been shown to influence the development of the autoimmune disease insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse. In human IDDM it has been suggested that the presence of an aspartate at position 57 of the DQ beta-chain might be important in determining resistance to development of IDDM. The involvement of MHC class II genes in IDDM was investigated through the introduction of MHC encoding transgenes. We show that introduction of a mutated I-Ag7 Ab gene which encodes an aspartate at position 57 reduces the incidence of IDDM but does not prevent insulitis, sialadenitis, or the development of insulin and nuclear autoantibodies.
Quartey-Papafio
R
R
Department of Pathology, University of Cambridge, United Kingdom.
Lund
T
T
Chandler
P
P
Picard
J
J
Ozegbe
P
P
Day
S
S
Hutchings
P R
PR
O'Reilly
L
L
Kioussis
D
D
Simpson
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001224:Aspartic Acid / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D003520:Cyclophosphamide; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D012793:Sialadenitis / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection / Q000235:genetics
D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D001224:Aspartic Acid; D003520:Cyclophosphamide