Abstract
Antigenic stimulation is associated with enhanced adhesion between T cells and antigen-presenting cells (APC). Binding of ligands to the T cell antigen receptor activates the adhesion function of lymphocyte function-associated molecule 1 (LFA-1; CD11a/CD18). We demonstrate here that ligand binding to major histocompatibility complex class II (Ia) molecules also activates LFA-1 function, providing a reciprocal mechanism for the induction of adhesion between T cells and Ia+ APC. Adhesion was affected by a qualitative change in LFA-1 molecules and was reversed by the protein kinase C inhibitor sphingosine. These results define a novel role for Ia molecules as signal transducing receptors that regulate LFA-1-dependent adhesion via a putative, Ia- coupled protein kinase(s).
Full Text
The Full Text of this article is available as a PDF (448.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Chatila T. A., Geha R. S., Arnaout M. A. Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules. J Cell Biol. 1989 Dec;109(6 Pt 2):3435–3444. doi: 10.1083/jcb.109.6.3435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dustin M. L., Springer T. A. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989 Oct 19;341(6243):619–624. doi: 10.1038/341619a0. [DOI] [PubMed] [Google Scholar]
- Hannun Y. A., Bell R. M. Functions of sphingolipids and sphingolipid breakdown products in cellular regulation. Science. 1989 Jan 27;243(4890):500–507. doi: 10.1126/science.2643164. [DOI] [PubMed] [Google Scholar]
- Inaba K., Steinman R. M. Monoclonal antibodies to LFA-1 and to CD4 inhibit the mixed leukocyte reaction after the antigen-dependent clustering of dendritic cells and T lymphocytes. J Exp Med. 1987 May 1;165(5):1403–1417. doi: 10.1084/jem.165.5.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kupfer A., Singer S. J. Cell biology of cytotoxic and helper T cell functions: immunofluorescence microscopic studies of single cells and cell couples. Annu Rev Immunol. 1989;7:309–337. doi: 10.1146/annurev.iy.07.040189.001521. [DOI] [PubMed] [Google Scholar]
- Marlin S. D., Springer T. A. Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell. 1987 Dec 4;51(5):813–819. doi: 10.1016/0092-8674(87)90104-8. [DOI] [PubMed] [Google Scholar]
- Mourad W., Scholl P., Diaz A., Geha R., Chatila T. The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction. J Exp Med. 1989 Dec 1;170(6):2011–2022. doi: 10.1084/jem.170.6.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nong Y. H., Remold-O'Donnell E., LeBien T. W., Remold H. G. A monoclonal antibody to sialophorin (CD43) induces homotypic adhesion and activation of human monocytes. J Exp Med. 1989 Jul 1;170(1):259–267. doi: 10.1084/jem.170.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruscetti F. W., Morgan D. A., Gallo R. C. Functional and morphologic characterization of human T cells continuously grown in vitro. J Immunol. 1977 Jul;119(1):131–138. [PubMed] [Google Scholar]
- Sanders V. M., Snyder J. M., Uhr J. W., Vitetta E. S. Characterization of the physical interaction between antigen-specific B and T cells. J Immunol. 1986 Oct 15;137(8):2395–2404. [PubMed] [Google Scholar]
- Scholl P. R., Diez A., Geha R. S. Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 bind to distinct sites on HLA-DR and HLA-DQ molecules. J Immunol. 1989 Oct 15;143(8):2583–2588. [PubMed] [Google Scholar]
- Scholl P., Diez A., Mourad W., Parsonnet J., Geha R. S., Chatila T. Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4210–4214. doi: 10.1073/pnas.86.11.4210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Kooyk Y., van de Wiel-van Kemenade P., Weder P., Kuijpers T. W., Figdor C. G. Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes. Nature. 1989 Dec 14;342(6251):811–813. doi: 10.1038/342811a0. [DOI] [PubMed] [Google Scholar]