L1 adhesion molecule on human lymphocytes and monocytes: expression and involvement in binding to alpha v beta 3 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 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.
Tumor Immunology Programme, German Cancer Research Center, Heidelberg, Germany.
O
O
Ebeling
A
A
Duczmal
S
S
Aigner
C
C
Geiger
S
S
Schöllhammer
J T
JT
Kemshead
P
P
Möller
R
R
Schwartz-Albiez
P
P
Altevogt
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion; D003001:Cloning, Molecular; D005091:Exons; D005796:Genes; D006410:Hematopoiesis; D006801:Humans; D039564:Integrin alphaV; D039661:Integrin beta3; D039841:Leukocyte L1 Antigen Complex; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism
D015703:Antigens, CD; D039564:Integrin alphaV; D039661:Integrin beta3; D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules; D009842:Oligopeptides; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; C047981:arginyl-glycyl-aspartic acid