Binding of T lymphocytes to hippocampal neurons through ICAM-5 (telencephalin) and characterization of its interaction with the leukocyte integrin CD11a/CD18.
Intercellular adhesion molecule-5 (ICAM-5, telencephalin) is a member of the immunoglobulin superfamily expressed on telencephalic neurons, and serves as a ligand for the leukocyte integrin CD11 a/CD18. We studied here the binding site in ICAM-5 for CD11a/CD18. Protein constructs containing the first immunoglobulin domain of ICAM-5 were able to support CD11a/CD18 interaction, while deletion of the first domain abolished binding. Monoclonal antibodies reacting with the first domain of ICAM-5 also completely blocked the interaction. The soluble first domain of ICAM-5 inhibited the binding of T cells to immobilized ICAM-5 at concentrations of 50 nM and higher. Interestingly, the sixth domain of ICAM-5 was also able to support leukocyte binding, but this binding activity may not involve leukocyte integrins. To test the involvement of ICAM-5 in leukocyte-neuron interactions, an assay using human T cells binding to rat hippocampal neurons was established. This binding was blocked by monoclonal antibodies against CD11a/CD18 and ICAM-5. Thus ICAM-5 may act as a major adhesion molecule for leukocyte binding to neurons in the central nervous system.
Tian
L
L
Department of Biosciences, University of Helskinki, Finland.
Kilgannon
P
P
Yoshihara
Y
Y
Mori
K
K
Gallatin
W M
WM
Carpén
O
O
Gahmberg
C G
CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D018821:CD18 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D006624:Hippocampus / Q000276:immunology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000276:immunology*; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; C086747:ICAM5 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D011993:Recombinant Fusion Proteins