Binding of T lymphocytes to hippocampal neurons through ICAM-5 (telencephalin) and characterization of its interaction with the leukocyte integrin CD11a / CD18

Abstract

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 CD11a/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.

The second domain of intercellular adhesion molecule-1 (ICAM-1) maintains the structural integrity of the leucocyte function-associated antigen-1 (LFA-1) ligand-binding site in the first domain

“…For ICAM-3, which is expected to have a similar domain 1-binding surface to ICAM-1, chimaeric constructs and mutations in domains 1 and 2 indicate that, as our data suggests for ICAM-1, the first domain of ICAM-3 contains the complete LFA-1-binding site [26,40,41]. A recent study of ICAM-5 using domain deletion constructs and mapped mAbs indicates that, for ICAM-5 also, only the first domain is required for binding LFA-1 [42]. Therefore location of the LFA-1-binding site solely in domain 1 seems to be a common feature for the ICAMs.…”

Identification of a Negatively Charged Peptide Motif within the Catalytic Domain of Progelatinases That Mediates Binding to Leukocyte β2 Integrins

“…As THP-1 cells do not express high amounts of the ␣ L chain (11), we examined the Jurkat T cell line, which expresses more ␣ L than ␣ M (28). We observed a significant immunoprecipitation of ␣ L by MMP-9 and MMP-2 antibodies after PDBu activation (Fig.…”

“…Cell Culture-The human HT1080 fibrosarcoma and THP-1 and Jurkat leukemic lines were obtained from ATCC and maintained as described previously (11,25,28). OCI/AML-3, derived from the primary blasts of an AML patient (29), was maintained in 10% fetal bovine serum/RPMI supplemented with L-glutamine, penicillin, and streptomycin.…”

“…The integrins were eluted at pH 11.5 in the presence of 2 mM MgCl 2 and 1% n-octyl glucoside as described previously (28).…”

A Novel Phenylalanine-Based Targeting Signal Directs Telencephalin to Neuronal Dendrites

“…TLCN can bind also to ␣L␤2 integrin [lymphocyte function-associated antigen-1 (LFA-1); CD11a/CD18] expressed by leukocytes and microglia. The binding between TLCN and LFA-1 may be important for the neuron/microglia or neuron/lymphocyte interactions under pathological conditions Tian et al, 1997Tian et al, , 2000a. Thus, the knowledge of dendritic sorting of TLCN would provide an important basis for understanding the roles of TLCN in a variety of dendritic functions in the telencephalic neurons.…”