Competitive binding to 1 using GAD65 as a specific
competitor. (a) Chemical structures of 1 and 3. (b) Serum from pooled Swiss or NOR9 serum (500 μg mL–1) was incubated with 1 immobilized onto
10 μm TentaGel beads in a blocking buffer with no soluble competitor
(black bars). Binding was monitored by flow cytometry after incubating
the beads with Alexa Fluor 647-conjugated secondary antibody. Competitive
binding (gray bars) to 1 was performed by preincubating
500 μg mL–1 NOR9 serum with 500 nM of either
soluble 1, 3, insulin, murine GAD65 containing
a GST fusion tag (mGAD65), or human GAD65 containing a GST fusion
tag (hGAD65). (c) Binding to TentaGel beads containing 3 was performed by diluting pooled Swiss or NOD4 serum to 500 μg
mL–1 in a blocking buffer (black bars). Competition
binding to 3 (gray bars) was performed in the presence
of 500 nM insulin or mGAD65. (d) Sera from two false positive samples,
Swiss8 and Swiss10, and one true positive sample, NOD7, were diluted
to 500 μg mL–1 and incubated in the presence
of 500 nM 3, insulin, and murine GAD65 lacking a GST
fusion tag (GAD65) for 5 min before incubating with immobilized 1 for 2 h. Beads were probed with Alexa Fluor 647-conjugated
secondary antibody, and binding was quantified by flow cytometry.
In all cases, data are reported as the mean ± s.d. from three
experiments. Statistical significance was determined using an unpaired t test: *P < 0.05; **P < 0.01; ***P < 0.001; ns = not significant.