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 th e immunoglobulin superfamily expressed on telencephalic neurons, and serves as a ligand for the leukocyte integrin CD11a/CD18. We studied here the bin ding site in ICAM-5 for CD11a/CD18. Protein constructs containing the first immunoglobulin domain of ICAM-5 were able to support CD11a/CD18 interactio n, while deletion of the first domain abolished binding. Monoclonal antibod ies reacting with the first domain of ICAM-5 also completely blocked the in teraction. The soluble first domain of ICAM-5 inhibited the binding of T ce lls to immobilized ICAM-5 at concentrations of 50 nM and higher. interestin gly 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 huma n T cells binding to rat hippocampal neurons was established. This binding was blocked by monoclonal antibodies against CD11a/CD18 and ICAM-5. Thus IC AM-5 may act as a major adhesion molecule for leukocyte binding to neurons in the central nervous system.