Ebeling O, Duczmal A, Aigner S, Geiger C, Schöllhammer S, Kemshead J T, Möller P, Schwartz-Albiez R, Altevogt P
Tumor Immunology Programme, German Cancer Research Center, Heidelberg, Germany.
Eur J Immunol. 1996 Oct;26(10):2508-16. doi: 10.1002/eji.1830261035.
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 alpha v beta 3 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 alpha v beta 3 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 approximately 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 (alpha v beta 3hi, alpha 5 beta 1lo) tumor cells and this binding was blocked by alpha v-specific mAb. In contrast, human Nalm-6 cells (alpha v beta 3lo, alpha 5 beta 1hi) 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 alpha v beta 3 and that its presence on leukocytes could be important for adhesion and migration.
L1黏附分子是免疫球蛋白（Ig）超家族的成员，最初在神经系统中被鉴定出来，它含有六个Ig样结构域。除了已知的L1-L1同型相互作用外，最近发现L1在小鼠中与极晚期抗原（VLA）-5结合，在人类中与αvβ3结合。第六个Ig结构域对该功能至关重要。我们现在证明，人类CD4+外周血T淋巴细胞、单核细胞和B淋巴细胞表达L1，但CD8+T淋巴细胞不表达。与T淋巴细胞上αvβ3的另一种配体CD31的表达相比，只有一小部分细胞是CD31+L1+双阳性。在人类单核细胞和淋巴瘤细胞系表面也检测到L1，其分子量约为220 kDa，与神经母细胞瘤细胞上的分子相似。我们还研究了人类L1第六个Ig结构域作为整合素配体的功能。使用源自第六个Ig结构域的含RGD肽以及L1第六个Ig结构域与人类IgG1的Fc部分的融合蛋白（6.L1-Fc），我们证明了人类MED-B1（αvβ3高表达，α5β1低表达）肿瘤细胞的结合，并且这种结合被αv特异性单克隆抗体阻断。相比之下，人类Nalm-6细胞（αvβ3低表达，α5β1高表达）不与6.L1-Fc融合蛋白结合。MED-B1细胞也可以用6.L1-Fc融合蛋白染色。我们的结果表明，人类L1主要与αvβ3结合，其在白细胞上的存在可能对黏附和迁移很重要。
