Gluten sensitivity typically presents as celiac disease, a common chronic small intestinal disorder. However, in certain individuals it is associated with dermatitis herpetiformis, a blistering skin disease characterized by granular IgA deposits in the papillary dermis. While tissue transglutaminase has been implicated as the major autoantigen of gluten sensitive disease, there has been no explanation as to why this condition appears in two distinct forms. Here we show that while sera from patients with either form of gluten sensitive disease react both with tissue transglutaminase and the related enzyme epidermal (type 3) transglutaminase, antibodies in patients having dermatitis herpetiformis show a markedly higher avidity for epidermal transglutaminase. Further, these patients have an antibody population specific for this enzyme. We also show that the IgA precipitates in the papillary dermis of patients with dermatitis herpetiformis, the defining signs of the disease, contain epidermal transglutaminase, but not tissue transglutaminase or keratinocyte transglutaminase. These findings demonstrate that epidermal transglutaminase, rather than tissue transglutaminase, is the dominant autoantigen in dermatitis herpetiformis and explain why skin symptoms appear in a proportion of patients having gluten sensitive disease.

The ability of laminins to self-polymerize is crucial for the formation of basement membranes. Development of this polymerized network has profound effects upon tissue architecture as well as on the intracellular organization and differentiation of neighboring cells. The laminin N-terminal (LN) domains have been shown to mediate this interaction and studies using proteolytic fragments derived from laminin-1 led to the theory that network assembly depends on the formation of a heterotrimeric complex between LN domains derived from ␣, ␤, and ␥ chains in different laminin molecules with homologous interactions being insignificant. The laminin family consists of 15 known isoforms formed from five ␣, three ␤, and three ␥ chains, of which some are truncated and lack the N-terminal LN domain. To address whether the model of heterotrimeric complex formation is applicable to laminin isoforms other than laminin-1, eight LN domains found in the laminin protein family were recombinantly expressed and tested in three different assays for homologous and heterologous interactions. The results showed that the lack of homologous interactions is an exception, with such interactions being seen for LN domains derived from all ␣ chains and from the ␤ 2 and ␤ 3 subunits. The ␥ chain-derived LN domains showed a far more limited binding repertoire, particularly in the case of the ␥ 3 chain, which is found present in a range of non-basement membrane locations. Further, whereas the interactions depended upon Ca 2؉ ions, with EDTA reversibly abrogating binding, EDTA-induced conformational changes were not reversible. Together these results demonstrate that the assembly model proposed on the basis of laminin-1 may be a simplification, with the assembly of naturally occurring laminin networks being far more complex and highly dependent upon which laminin isoforms are present.Basement membranes are specialized extracellular matrices found underlying all epithelia and endothelia as well as surrounding many types of mesenchymal cells. Laminins constitute the major noncollagenous protein component within the basement membrane and are crucial for its formation (1, 2). Through their interactions with specific receptors, especially members of the ␤ 1 integrin family and ␣-dystroglycan, they induce many cellular effects, including differentiation and cellular and axonal migration. The prototype, laminin-1, isolated from embryonic carcinoma cells (3) or the Engelbreth-HolmSwarm tumor (4) has been shown to belong to a family consisting of 15 members (for nomenclature, see Refs. 5-7). Laminins are multidomain heterotrimers formed by the combination of one ␣, one ␤, and one ␥ chain. Laminin-1 is an 800-kDa glycoprotein composed of a 400-kDa ␣ 1 chain and ␤ 1 and ␥ 1 chains, each of 200 kDa. It has a cross structure with one long and three short arms, the latter being formed from the three free N-terminal ends of the ␣, ␤, and ␥ chains (8). These parts of the ␤ and ␥ chains each contain two globular domains, designated IV and VI, whereas there are three...

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A cDNA fragment coding for the sex-inducing glycoprotein of Volvox carreri f. nuguriensis was expressed in a mammalian cell system (baby hamster kidney (BHK) cells). The transfection product exhibited a specific biological activity intermediate between the natural pheromone of the strains Volvox curterz f. nuguriensis and Volvox curteri f. weismunniu. Immunoblot analysis showed that the sex-inducing activity was expressed as a set of three iso-glycoproteins (35, 34 and 31 kDa).