Abstract
THE co-ordinated function of effector and accessory cells in the immune system is assisted by adhesion molecules on the cell surface that stabilize interactions between different cell types1. Leukocyte function-associated antigen 1 (LFA-1) is expressed on the surface of all white blood cells2 and is a receptor for intercellular adhesion molecules (ICAM) 1 and 2 (ref. 3) which are members of the immunoglobulin superfamily4–6. The interaction of LFA-1 with ICAMs 1 and 2 provides essential accessory adhesion signals in many immune interactions, including those between T and B lymphocytes7 and cytotoxic T cells and their targets8,9. In addition, both ICAMs are expressed at low levels on resting vascular endothelium10; 1C AM-1 is strongly upregulated by cytokine stimulation and plays a key role in the arrest of leukocytes in blood vessels at sites of inflammation and injury. Recent work has indicated that resting leukocytes express a third ligand, ICAM-3, for LFA-1 (refs 11,12). ICAM-3 is potentially the most important ligand for LFA-1 in the initiation of the immune response because the expression of ICAM-1 on resting leukocytes is low. We report the expression cloning of a complementary DNA, pICAM-3, encoding a protein constitutively expressed on all leukocytes, which binds LFA-1. ICAM-3 is closely related to ICAM-1, consists of five immunoglobulin domains, and binds LFA-1 through its two N-terminal domains.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Dustin, M. L. & Springer, T. A. A. Rev. Immun. 9, 27–66 (1991).
Uciechowski, P. & Schmidt, R. E. in Leucocyte Typing IV. White Cell Differentiation Antigens (eds Knapp, W.) 543–554 (Oxford Univ. Press. Oxford, 1989).
Marlin, S. D. & Springer, T. A. Cell 51, 813–819 (1987).
Simmons, D. L., Makgoba, M. W. & Seed, B. Nature 331, 624–627 (1988).
Staunton, D. E., Marlin, S. D., Stratowa, C., Dustin, M. L. & Springer, T. A. Cell 52, 925–933 (1988).
Staunton, D. E., Dustin, M. L. & Springer, T. A. Nature 339, 61–64 (1989).
Moy, V. T. & Brian, A. A. J. exp. Med. 175, 1–7 (1992).
Altmann, D. M., Hogg, N., Trowsdale, J. & Wilkinson, D. Nature 338, 521–514 (1989).
Makgoba, M. W. et al. Eur. J. Immun. 18, 637 (1988).
Needham, L., Pearson, J. D. & Hellewell, P. G. in Vascular Endothelium: Interactions with Circulating Cells (eds Gordon, J. L.) 61–89 (Elsevier, Amsterdam, 1991).
de Fougerolles, A. R., Stacker, S. A., Schwarting, R. & Springer, T. A. J. exp. Med. 174, 253–267 (1991).
de Fougerolles, A. R. & Springer, T. A. J. exp. Med. 175, 185–190 (1992).
Knapp, W. et al. Leucocyte Typing IV. White Cell Differentiation Antigens (Oxford Univ. Press, Oxford, 1989).
Seed, B. & Aruffo, A. Proc. natn. Acad. Sci. U.S.A. 84, 8573–8577 (1987).
Cavener, D. R. & Ray, S. C. Nucleic Acids Res. 19, 3185–3192 (1991).
von Heijne, G. Nucleic Acids Res. 14, 4683 (1986).
Staunton, D. E., Dustin, M. L., Erickson, H. P. & Springer, T. A. Cell 61, 243–254 (1990).
Berendt, A. R. et al. Cell 68, 71–81 (1992).
Dransfield, I., Cabanas, C., Barrett, J. & Hogg, N. J. Cell Biol. 116, 1527–1535 (1992).
Dustin, M. L. & Springer, T. A. Nature 341, 619 (1989).
Cosimi, A. B. et al. J. Immun. 144, 4604–4612 (1990).
Flavin, T., Rothlein, R. Faanes, R., Ivens, K. & Starnes, V. A. Transpl. Proc. 23, 533–534 (1991).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Devereux, J., Haeberli, P. & Smithies, O. Nucleic Acids Res. 12, 387–395 (1984).
Simmons, D. L. & Needham, L. in Vascular Endothelium: Interactions with Circulating Cells (eds Gordon, J. L.) 1–32 (Elsevier, Amsterdam, 1991).
Lehmann, J. G., Riehtmuller, G. & Johnson, J. P. Proc. natn. Acad. Sci. U.S.A. 86, 9891–9895 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fawcett, J., Holness, C., Needham, L. et al. Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes. Nature 360, 481–484 (1992). https://doi.org/10.1038/360481a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/360481a0
- Springer Nature Limited
This article is cited by
-
Comprehensive genotyping analysis of single nucleotide polymorphisms responsible for beef marbling in Japanese Black cattle
BMC Genomic Data (2024)
-
A survey of endogenous retrovirus (ERV) sequences in the vicinity of multiple sclerosis (MS)-associated single nucleotide polymorphisms (SNPs)
Molecular Biology Reports (2016)
-
Novel role of ICAM3 and LFA-1 in the clearance of apoptotic neutrophils by human macrophages
Apoptosis (2013)
-
Asn54-linked glycan is critical for functional folding of intercellular adhesion molecule-5
Glycoconjugate Journal (2012)
-
The CD11a partner in Sus scrofa lymphocyte function-associated antigen-1 (LFA-1): mRNA cloning, structure analysis and comparison with mammalian homologues
BMC Veterinary Research (2005)