Costimulation of T cell receptor-triggered IL-2 production by Jurkat T cells via fibroblast growth factor receptor 1 upon its engagement by CD56.
Recent studies have demonstrated that neural cell adhesion molecule (NCAM) is involved in multiple adhesive interactions with several different classes of ligands on the cell surface and in the extracellular matrix. One of these ligands is fibroblast growth factor receptor (FGFR) that is expressed on neural cells. While it is known that CD56 is a molecular isoform of NCAM expressed on human NK cells and a subset of T cells, it remains poorly characterized, with its ligand unidentified. Therefore, we were prompted to examine if CD56 molecules on NK cells interact with FGFR expressed on T cells. We demonstrate that ligation of FGFR1 beta on J.C2-14 Jurkat T cells by CD56 on fixed NK-92 cells costimulates TCR/CD3-triggered IL-2 production. CD56-binding mAbs inhibited the costimulatory effect of NK-92 cells in 50-75%. Flow cytometric analysis and cell adhesion assays showed that FGFR1 beta/Fc and FGFR2 beta/Fc chimeric proteins bind to NK-92 cells. The binding of FGFR1 beta/Fc protein to CD56 molecules was verified by immunoprecipitation of CD56 with anti-CD56 mAb followed by Western blotting with FGFR1 beta/Fc. These findings suggest that ligation of FGFR1 by CD56 may contribute to the interaction between NK cells and T cells that we have postulated in our previous studies.
Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA. fjkos@beckman.com
Ferdynand J
FJ
Kos
Cynthia S
CS
Chin
D019002:CD56 Antigen / Q000378:metabolism*; D002460:Cell Line; D018920:Coculture Techniques; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D019002:CD56 Antigen; D007141:Immunoglobulin Fc Fragments; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2