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Suman Kumari, Kailash C. Bhol, Raymond K. Simmons, Mohammed S. Razzaque, Erik Letko, C. Stephen Foster, A. Razzaque Ahmed; Identification of Ocular Cicatricial Pemphigoid Antibody Binding Site(s) in Human β4 Integrin. Invest. Ophthalmol. Vis. Sci. 2001;42(2):379-385.
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purpose. To identify specific site(s) on human β4 molecule to which sera from
ocular cicatricial pemphigoid (OCP) patients bind and to determine its
role in the process of blister formation.
methods. Clone the fragments representing the extracellular and intracellular
domain of β4 molecule from normal human conjunctival mRNA into an
expression vector; map the region to which sera from OCP patients bind
by Western blot analysis. Determine the role of the immunodominant
region in pathogenesis by demonstrating the ability of the rabbit
antibody to the immunodominant region to produce separation of basement
membrane zone (BMZ) from the basal epithelial layer when incubated with
normal human conjunctiva in an in vitro organ culture model.
results. Majority of the OCP sera tested bound to the C-terminal end of the
intracellular domain (IC3.0) of the human β4 integrin. Further
subcloning of IC3.0 demonstrated that a smaller fragment extending from
1489 aa to 1572 aa (IC3.4) was responsible for this binding. This
region may have multiple antibody binding sites. Antibody to human
IC3.0 and IC3.4 produced in rabbit, resulted in BMZ separation,
histologically identical with that observed when normal human
conjunctiva was cultured with OCP sera in an human conjunctival organ
conclusions. These observations identify IC3.4 as the antibody binding site for sera
of OCP patients and suggest a possible role for it in blister
formation. Indirectly it highlights certain important aspects of the
structural and functional dynamics of the biology of the hemidesmosomes
and basement membranes.
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