Immunochemical characterization of several differentiation-dependent epidermal antigens, with special emphasis on a keratinocyte-specific form of desmoglein

• Main Author: Loomis, Cynthia Ann
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-1990
• Subjects: Biology; Cellular biology
• ISBN: 9798207463254

The epidermis is a complex, self-renewing epithelium which consists of four histologically distinct zones--the basal, spinous, granular and cornified cell layers. In an ongoing effort to better understand the mechanisms involved in sorting more differentiated keratinocytes into successive cell layers, I generated a panel of monoclonal antibodies to stage-specific epidermal antigens as well as to extracellular domains of potential cell adhesion molecules. In this thesis, I describe two studies that I conducted using eight of these antibodies. In the first study, I characterized a monoclonal antibody, AE23, which reacts with an extracellular epitope of a 160-kD epidermal protein. Based on a number of biochemical and immunological criteria, this antigen is indistiguishable from epidermal desmoglein, a glycoprotein component of desmosomes. Using AE23 and another monoclonal antibody, DG3.4, I constructed a preliminary topographic map of this epidermal adhesion protein. Interestingly, differential tissue expression of these two epitopes indicated desmoglein is not a single homogeneous protein species, but consists of closely related isoforms. Although the function of the tissue-specific variation defined by AE23 remains to be defined, preliminary cell culture data suggested it may be involved in desmosomal maturation. In the second study, I examined the "flexibility" of epidermal differentiation. Using monoclonal antibodies to the K1/K10 keratins and to the "more advanced" differentiation marker filaggrin, I demonstrated that the expression of these two sets of protein markers is not obligatorily coupled as suggested by in vivo expression patterns.