TABLE 1

Panel of 11 human mAbs to GAD65 derived from two patients with type 1 diabetes and one with autoimmune polyendocrine syndrome type 2 with corresponding epitope data

mAbSource*Epitope regionMutants of GAD65 that affect reactivity
COOH-terminus
    M3Type 1 diabetes i483–499, 556–585N483A, H568Q
    DPAType 1 diabetes ii483–499, 556–585H568Q
    M2Type 1 diabetes i514–528E517P, E520P
    M5Type 1 diabetes i512–540E517P, E520P, E521Q, S524E, S527H, V532K
    b78APS-2532–540, 514–528V532K, S524A/R525A/L526A§
NH2-terminus
    DPDType 1 diabetes ii96–173No data
    DPBType 1 diabetes ii1–102No data
PLP domain
    b96.11APS-2308–365R357A/K376A, F344A, D305A/E306A/R307A, K498A/P499A/Q500A
    M4Type 1 diabetes i308–365K358N
    M6Type 1 diabetes i242–282E264
PLP and NH2-terminus
    DPCType 1 diabetes ii134–242, 366–413P231S/S234D
  • *

    * Derivation of mAbs according to Richter et al. (6) for type 1 diabetes i, Madec et al. (7) for type 1 diabetes ii, and Tremble et al. (8) autoimmune polyendocrine syndrome type 2 (APS-2). From data on epitope regions on linear sequence of GAD65 and GAD65 mutants according to

  • Schwartz et al. (4),

  • Powers et al. (9),

  • §

    § O'Connor et al. (10), and

  • Fenalti et al. (11).

  • Binding not affected by mutation of GAD65 E264T, but mutation of GAD67 T273E conferred 50% reactivity (4).