Abstract
This study compares the biochemical responses in T cells activated with the CD28 ligands B7-1 and B7-2. The patterns of tyrosine phosphorylation induced in T cells by these two CD28 ligands are identical, but clearly different from the tyrosine phosphorylation induced by the T cell receptor (TCR). The TCR regulates protein complexes mediated by the adapter Grb2 both in vivo and in vitro. In contrast, there is no apparent regulation of in vivo Grb2 complexes in response to B7-1 or B7-2. Rather, B7-1 and B7-2 both induce tyrosine phosphorylation of a different adaptor protein, p62. The regulation of p62 is a unique CD28 response that is not shared with the TCR. These data indicate that B7-1 and B7-2 induce identical tyrosine kinase signal transduction pathways. The data show also that the TCR and CD28 couple to different adapter proteins, which could explain the divergence of TCR and CD28 signal transduction pathways during T cell activation.
Highlights
§ To whom correspondence should be addressed: Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, Rm. 615, 44 Lincoln’s Inn Fields, London WC2A 3PX, United Kingdom
To examine whether B7-2/B70 can induce tyrosine phosphorylation of cellular substrates, a Western blot of cell lysates prepared from cells treated with CD28 antibody CD28.2, or B7-1, B7-2, or B70 L cells, or from untransfected L cells was probed with an anti-phosphotyrosine antibody
B7-1- and B7-2induced patterns of tyrosine phosphorylation are different than the T cell receptor (TCR) stimulation pattern, which supports the hypothesis that CD28 and the TCR regulate different cellular protein-tyrosine kinases (PTKs)
Summary
§ To whom correspondence should be addressed: Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, Rm. 615, 44 Lincoln’s Inn Fields, London WC2A 3PX, United Kingdom. Triggering of the CD28 receptor with antibodies induces phospholipase C and Ras activation [18, 19]. CD28 stimulation by the natural ligand B7-1 does not induce phospholipase C activity or Ras activation, but is associated with activation of phosphatidylinositol 3Ј-kinase [19, 24]. In TCR-stimulated cells, there is rapid formation of a complex between Sos/Grb and a 36-kDa membrane protein that is a substrate for TCR-induced PTKs [27]. Grb may be important in coupling the TCR to more than just Sos/p21ras because additional Grb effector molecules have been identified in T cells. Ligation of CD28 with antibodies has been shown to induce tyrosine phosphorylation of the Grb2-associated p36 molecule, whereas triggering of CD28 with the natural ligand B7-1, which activates cellular PTKs, does not [19]. It is possible that the effects of the CD28 antibodies on p36 phosphorylation mimic the effects of the ligand B7-2/B70 triggering of CD28
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
