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E
7, But Not for Homophilic Adhesion








* Project Research Laboratory, Research Center for Genomic Medicine and
Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama, Japan; and
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
The integrin
E
7 is expressed on intestinal intraepithelial T lymphocytes and CD8+ T lymphocytes in inflammatory lesions near epithelial cells. Adhesion between
E
7+ T and epithelial cells is mediated by the adhesive interaction of
E
7 and E-cadherin; this interaction plays a key role in the damage of target epithelia. To explore the structure-function relationship of the heterophilic adhesive interaction between E-cadherin and
E
7, we performed cell aggregation assays using L cells transfected with an extracellular domain-deletion mutant of E-cadherin. In homophilic adhesion assays, L cells transfected with wild-type or a domain 5-deficient mutant formed aggregates, whereas transfectants with domain 1-, 2-, 3-, or 4-deficient mutants did not. These results indicate that not only domain 1, but domains 2, 3, and 4 are involved in homophilic adhesion. When
E
7+ K562 cells were incubated with L cells expressing the wild type, 23% of the resulting cell aggregates consisted of
E
7+ K562 cells. In contrast, the binding of
E
7+ K562 cells to L cells expressing a domain 5-deficient mutant was significantly decreased, with
E
7+ K562 cells accounting for only 4% of the cell aggregates, while homophilic adhesion was completely preserved. These results suggest that domain 5 is involved in heterophilic adhesion with
E
7, but not in homophilic adhesion, leading to the hypothesis that the fifth domain of E-cadherin may play a critical role in the regulation of heterophilic adhesion to
E
7 and may be a potential target for treatments altering the adhesion of
E
7+ T cells to epithelial cells in inflammatory epithelial diseases.
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