Association of intercellular adhesion molecule 1 with the multichain high-affinity interleukin 2 receptor.
Previously, using flow cytometric resonance energy transfer and lateral diffusion measurements, we demonstrated that a 95-kDa protein identified by two monoclonal antibodies (OKT27 and OKT27b) interacts physically with the 55-kDa alpha protein of the high-affinity interleukin 2 (IL-2) receptor. In the present study, this 95-kDa protein (p95) was purified and amino acid sequence data were obtained that showed strong homology to the human intercellular adhesion molecule 1 (ICAM-1). The identity of the p95 protein with ICAM-1 was confirmed by sequential immunoprecipitations using OKT27 and an antibody, WEHI-CAM-1, that is directed toward ICAM-1. We confirmed the physical proximity of p95/ICAM-1 to the IL-2 receptor alpha subunit by demonstrating that radiolabeled IL-2 could be cross-linked to this protein expressed on activated T cells. In functional studies, the antibodies OKT27 and OKT27b inhibited T-cell proliferative responses to OKT3, to soluble antigen, and to heterologous cells (mixed lymphocyte reaction). However, these antibodies did not inhibit IL-2-induced proliferation of an IL-2-dependent T-cell line. Taken together with our previous observations, the present studies suggest that ICAM-1 is in proximity and interacts physically with the high-affinity IL-2 receptor. The association of ICAM-1 with the IL-2 receptor may facilitate the paracrine IL-2-mediated stimulation of T cells expressing IL-2 receptors by augmenting homotypic T-T-cell interaction, by receptor-directed focusing of IL-2 release by helper T cells, and by focusing IL-2 receptors of the physically linked cells to the site of lymphocyte function-associated antigen 1-ICAM-1-IL-2 receptor interaction.
Burton
J
J
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Goldman
C K
CK
Rao
P
P
Moos
M
M
Waldmann
T A
TA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000302:isolation & purification* / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008970:Molecular Weight; D015375:Receptors, Interleukin-2 / Q000302:isolation & purification* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1