Human insulin autoantibody fine specificity and H and L chain use.
Fine specificity and H and L chain isotypes of insulin autoantibodies in sera from 11 subjects were examined. None of these 11 subjects was treated with exogenous insulin. Two patterns of fine specificity were found. In one, the autoantibodies were specific for human insulin, with a requirement for threonine at B30. The conservative substitution in pork insulin (threonine to alanine) abrogated IgG binding by these sera. Insulin autoantibodies in other sera cross-reacted with beef, pork, and human insulin; not requiring threonine at B30. Reciprocal competitive inhibition experiments showed that epitopes recognized by the human specific insulin autoantibodies were exclusively on the B chain, whereas the cross-reactive sera contain autoantibodies that recognize both the B chain and combinatorial (A and B chain) epitopes. The fine specificity of cross-reactive insulin autoantibodies are thus similar to insulin antibodies from insulin-treated subjects. When IgG subclasses and L chains of insulin autoantibodies were examined, however, restricted C region usage was found. The hierarchy was IgG3 greater than G1 greater than G2 greater than G4; with one subclass dominant in each serum, although others were used. L chain use was similarly restricted. There was no correlation between isotype and fine specificity or between H and L chain type. It is concluded that heterogeneity of insulin autoantibodies is restricted. The response is probably more oligo- or pauciclonal than insulin antibody from insulin-treated subjects.
Nell
L J
LJ
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Hulbert
C
C
Thomas
J W
JW
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis* / Q000096:biosynthesis; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007330:Insulin Antibodies / Q000032:analysis* / Q000096:biosynthesis; D008969:Molecular Sequence Data; D011487:Protein Conformation
D001323:Autoantibodies; D000939:Epitopes; D007132:Immunoglobulin Isotypes; D007330:Insulin Antibodies