L1 adhesion molecule on human lymphocytes and monocytes: expression and involvement in binding to αvβ3 integrin

The L1 adhesion molecule is a member of the immunoglobulin (Ig) superfamily initially identified in the nervous system which contains six Ig‐like domains. Besides the known L1‐L1 homotypic interaction, L1 was recently shown to bind to very late antigen (VLA)‐5 in the mouse and αvβ3 in the human. The sixth Ig domain is critical for this function. We now demonstrate that human CD4+ peripheral blood T lymphocytes, monocytes and B lymphocytes, but not CD8+ T lymphocytes, express L1. When compared to the expression of CD31, another ligand for αvβ3 on T lymphocytes, only a small proportion of cells were CD31+L1+ double positive. L1 was also detected on the surface of human monocytic and lymphoid tumor lines and was shown to have a molecular mass of ∼220 kDa, similar to the molecule present on neuroblastoma cells. The function of the sixth Ig domain of human L1 as an integrin ligand was also investigated. Using an RGD‐containing peptide derived from the sixth Ig domain as well as a fusion protein of the sixth Ig domain of L1 and the Fc portion of human IgG1 (6.L1‐Fc), we demonstrated the binding of human MED‐B1 (αvβ3hi, α5β1lo) tumor cells and this binding was blocked by αv‐specific mAb. In contrast, human Nalm‐6 cells (αvβ3lo, α5β1hi) did not bind to the 6.L1‐Fc fusion protein. MED‐B1 cells could also be stained with the 6.L1‐Fc fusion protein. Our results suggest that human L1 binds predominantly to αvβ3 and that its presence on leukocytes could be important for adhesion and migration.

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