The relationship between the ectodomain shedding of the 180-kDa bullous pemphigoid antigen and its autoantigenicity

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The 180-kDa bullous pemphigoid antigen (BP180) is a hemidesmosomal transmembrane protein. The ectodomain of BP180 is shed from keratinocyte cell surface by a proteolytic cleavage within the membrane-proximal non-collagenous 16th A (NC16A) domain. The autoantigen for the major type of linear IgA bullous dermatosis (LAD, lamina lucida type) is the shed ectodomain of BP180. However, why most LAD sera react with the shed ectodomain, but not with the intact BP180, is unknown. The aim of this study was to characterize the unique cleavage-dependent epitope(s) in the shed ectodomain. Four of the six LAD sera reacted mainly to the boundary region between the NC16A and the collagenous 15th (C15) domains. The results of this study indicate that the major epitopes for LAD sera is formed or exposed by a cleavage-induced conformational change, and are located at the boundary between the NC16A and C15 domains.