PEMPHIGUS-VULGARIS ANTIGEN, A DESMOGLEIN TYPE OF CADHERIN, IS LOCALIZED WITHIN KERATINOCYTE DESMOSOMES

Pemphigus vulgaris antigen (PVA) is a member of the desmoglein subfami ly of cadherin cell adhesion molecules. Because autoantibodies in this disease cause blisters due to loss of epidermal cell adhesion, and be cause desmoglein is found in the desmosome cell adhesion junction, we wanted to determine if PVA is also found in desmosomes. By immunofluor escence, PV IgG bound, in a dotted pattern, to the cell surface of cul tured human keratinocytes induced to differentiate with calcium, sugge sting junctional staining. However, by preembedding, immunogold electr on microscopic studies only slight labeling could be detected in desmo somes, presumably because of difficulty in gold penetration of intact desmosomes. We therefore treated the keratinocytes with 0.01% trypsin in 1 mM calcium, conditions known to preserve cadherin antigenicity bu t that caused slight separation of desmosomes, before immunogold stain ing. In this case there was extensive labeling of the extracellular pa rt of desmosomes but not of the interdesmosomal cell membrane which wa s stained with anti-beta2-microglobulin antibodies. To confirm the spe cificity of this binding we showed that antibodies raised in rabbits a gainst the extracellular portions of PVA also bound desmosomes in thes e cultures. In intact mouse epidermis we could also show slight, but s pecific, immunogold desmosomal labeling with PV IgG. Furthermore, neon atal mice injected with PV IgG affinity purified on PVA showed desmoso mal separation with the IgG localized to desmosomal cores. These resul ts indicate that PVA is organized and concentrated within the desmosom e where it presumably functions to maintain the integrity of stratifyi ng epithelia.