Transcription factor jun-B is target of autoreactive T-cells in IDDM.
Target antigens defined by autoantibodies in IDDM include insulin, a putative glycolipid that reacts with islet cell antibodies, and a 64,000-M(r) protein recently identified as glutamic acid decarboxylase. In addition, some IDDM sera that contain antibodies to glutamic acid decarboxylase also coprecipitate a 38,000-M(r) protein from islets. This study used a high titer anti-38,000-M(r) serum to screen bacteriophage lambda cDNA expression libraries and identified human islet and placental clones encoding jun-B, the nuclear transcription protein, of predicted 38,000 M(r). Peripheral blood T-cells exhibited significant proliferation in response to a recombinant fragment of jun-B (amino acids 1-180) in 12 of 17 (71%) recent-onset IDDM subjects, 8 of 16 (50%) ICA-positive first-degree relatives of IDDM subjects who were at risk, 3 of 12 (25%) other autoimmune disease subjects, and 0 of 10 healthy control subjects. Proliferation to tetanus toxoid did not differ significantly between the groups. Responses to jun-B were not related to age, sex, or human leukocyte antigen status. Thus, autoreactive T-cells identify a novel antigen, p38 jun-B, in IDDM and appear to indicate subjects at risk for the development of clinical disease.
Honeyman
M C
MC
Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Cram
D S
DS
Harrison
L C
LC
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology*; D002648:Child; D003001:Cloning, Molecular; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006111:Graves Disease / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D001324:Autoantigens; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; C024211:islet cell antibody; D005982:Glutathione Transferase