RELATIONSHIP OF THE 37,000-M(R) AND 40,000-M(R) TRYPTIC FRAGMENTS OF ISLET ANTIGENS IN INSULIN-DEPENDENT DIABETES TO THE PROTEIN-TYROSINE PHOSPHATASE-LIKE MOLECULE IA-2 (ICA512)

被引:251
作者
PAYTON, MA [1 ]
HAWKES, CJ [1 ]
CHRISTIE, MR [1 ]
机构
[1] UNIV LONDON KINGS COLL,SCH MED & DENT,DEPT MED,LONDON SE5 9PJ,ENGLAND
关键词
INSULIN-DEPENDENT DIABETES; AUTOANTIGENS; AUTOANTIBODIES; PROTEIN TYROSINE PHOSPHATASE; GLYCOPROTEINS;
D O I
10.1172/JCI118188
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Sera from patients with insulin-dependent diabetes immunoprecipitate 64,000-M(r) proteins, distinct from glutamate decarboxylase, that are cleaved to 37,000- and 40,000-M(r) fragments by trypsin. We investigated possible relationships between 37,000- or 40,000-M(r) fragments of antigen and the tyrosine phosphatase-like protein, IA-2 (ICA512). Antibodies from nondiabetic relatives bound differentially to 37,000- and 40,000-M(r) fragments indicating presence of distinct epitopes, Precursors of these fragments could be separated on immobilized lectins, suggesting different carbohydrate content. Levels of antibodies to 40,000-M(r) fragments were strongly associated with those to the intracellular domain of IA-2. Recombinant intracellular domain of IA-2 blocked binding of antibodies to 40,000-M(r) fragments expressed by insulinoma cells and partially blocked binding to 37,000-M(r) fragments. Furthermore, trypsinization of recombinant intracellular domain of IA-2 generated proteolytic fragments of identical M(r) to the 40,000-M(r) fragments of insulinoma antigen; 37,000-M(r) fragments were not generated. Thus, 40,000-M(r) fragments of islet autoantigen are derived from a protein similar or identical to the tyrosine phosphatase-like molecule, IA-2. The 37,000-M(r) fragments are derived from a different, although related, protein.
引用
收藏
页码:1506 / 1511
页数:6
相关论文
共 27 条
[1]  
[Anonymous], 1994, PROGRAM MANUAL WISCO
[2]   REVELATION OF SPECIFICITY OF 64K AUTOANTIBODIES IN IDDM SERUMS BY HIGH-RESOLUTION 2-D GEL-ELECTROPHORESIS - UNAMBIGUOUS IDENTIFICATION OF 64K TARGET ANTIGEN [J].
BAEKKESKOV, S ;
WARNOCK, G ;
CHRISTIE, M ;
RAJOTTE, RV ;
LARSEN, PM ;
FEY, S .
DIABETES, 1989, 38 (09) :1133-1141
[3]   AUTOANTIBODIES IN NEWLY DIAGNOSED DIABETIC CHILDREN IMMUNOPRECIPITATE HUMAN PANCREATIC-ISLET CELL-PROTEINS [J].
BAEKKESKOV, S ;
NIELSEN, JH ;
MARNER, B ;
BILDE, T ;
LUDVIGSSON, J ;
LERNMARK, A .
NATURE, 1982, 298 (5870) :167-169
[4]  
BINGLEY PJ, 1994, DIABETES, V43, P1291
[5]  
Brunstedt J, 1984, METHODS DIABETES R C, P245
[6]   IDENTIFICATION AND CLONING OF A GRANULE AUTOANTIGEN (CARBOXYPEPTIDASE-H) ASSOCIATED WITH TYPE-I DIABETES [J].
CASTANO, L ;
RUSSO, E ;
ZHOU, L ;
LIPES, MA ;
EISENBARTH, GS .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1991, 73 (06) :1197-1201
[7]   ANTIBODIES TO A MR-64000 ISLET CELL PROTEIN IN SWEDISH CHILDREN WITH NEWLY DIAGNOSED TYPE-1 (INSULIN-DEPENDENT) DIABETES [J].
CHRISTIE, M ;
LANDINOLSSON, M ;
SUNDKVIST, G ;
DAHLQUIST, G ;
LERNMARK, A ;
BAEKKESKOV, S .
DIABETOLOGIA, 1988, 31 (08) :597-602
[8]   DETECTION OF PANCREATIC-ISLET 64,000 MR AUTOANTIGENS IN INSULIN-DEPENDENT DIABETES DISTINCT FROM GLUTAMATE-DECARBOXYLASE [J].
CHRISTIE, MR ;
HOLLANDS, JA ;
BROWN, TJ ;
MICHELSEN, BK ;
DELOVITCH, TL .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (01) :240-248
[9]   DISTINCT ANTIBODY SPECIFICITIES TO A 64-KD ISLET CELL ANTIGEN IN TYPE-1 DIABETES AS REVEALED BY TRYPSIN TREATMENT [J].
CHRISTIE, MR ;
VOHRA, G ;
CHAMPAGNE, P ;
DANEMAN, D ;
DELOVITCH, TL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (03) :789-794
[10]   ANTIBODIES TO ISLET 37K ANTIGEN, BUT NOT TO GLUTAMATE-DECARBOXYLASE, DISCRIMINATE RAPID PROGRESSION TO IDDM IN ENDOCRINE AUTOIMMUNITY [J].
CHRISTIE, MR ;
GENOVESE, S ;
CASSIDY, D ;
BOSI, E ;
BROWN, TJ ;
LAI, M ;
BONIFACIO, E ;
BOTTAZZO, GF .
DIABETES, 1994, 43 (10) :1254-1259