Alterations in tyrosine protein phosphorylation induced by antibody-mediated cross-linking of the CD4 receptor of T lymphocytes

1989 ◽  
Vol 9 (10) ◽  
pp. 4441-4446
Author(s):  
A Veillette ◽  
J B Bolen ◽  
M A Bookman
Keyword(s):  
T Cell ◽  
Protein Phosphorylation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cross Linking ◽  
Rapid Changes ◽  
Tyrosine Protein Kinase ◽  
Enzymatic Activation ◽  
Intracellular Signal ◽  
Carboxy Terminal

Accumulating data suggest that the CD4 T-cell surface antigen transduces an independent intracellular signal during antigen-mediated T-cell activation. CD4 is physically associated with the internal membrane tyrosine protein kinase p56lck and can mediate, after antibody-mediated cross-linking, the rapid enzymatic activation of Lck, implying that CD4 signalling may involve changes in tyrosine protein phosphorylation. In this report, we describe that cross-linking of CD4 results in a series of rapid changes in intracellular tyrosine protein phosphorylation. The most prominent CD4-induced tyrosine phosphorylation change involved p56lck, which became extensively phosphorylated on the carboxy-terminal tyrosine residue 505 and, to a lesser extent, lymphocytes can transduce an intracellular signal resulting in tyrosine protein phosphorylation and strongly suggest that this property of CD4 is mediated through p56lck.

scholarly journals Alterations in tyrosine protein phosphorylation induced by antibody-mediated cross-linking of the CD4 receptor of T lymphocytes.

1989 ◽  
Vol 9 (10) ◽  
pp. 4441-4446 ◽  
Author(s):  
A Veillette ◽  
J B Bolen ◽  
M A Bookman
Keyword(s):  
T Cell ◽  
Protein Phosphorylation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cross Linking ◽  
Rapid Changes ◽  
Tyrosine Protein Kinase ◽  
Enzymatic Activation ◽  
Intracellular Signal ◽  
Carboxy Terminal

Accumulating data suggest that the CD4 T-cell surface antigen transduces an independent intracellular signal during antigen-mediated T-cell activation. CD4 is physically associated with the internal membrane tyrosine protein kinase p56lck and can mediate, after antibody-mediated cross-linking, the rapid enzymatic activation of Lck, implying that CD4 signalling may involve changes in tyrosine protein phosphorylation. In this report, we describe that cross-linking of CD4 results in a series of rapid changes in intracellular tyrosine protein phosphorylation. The most prominent CD4-induced tyrosine phosphorylation change involved p56lck, which became extensively phosphorylated on the carboxy-terminal tyrosine residue 505 and, to a lesser extent, lymphocytes can transduce an intracellular signal resulting in tyrosine protein phosphorylation and strongly suggest that this property of CD4 is mediated through p56lck.

scholarly journals ICOS agonism by JTX-2011 (vopratelimab) requires initial T cell priming and Fc cross-linking for optimal T cell activation and anti-tumor immunity in preclinical models

PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0239595 ◽  
Author(s):  
Amanda Hanson ◽  
Kutlu Elpek ◽  
Ellen Duong ◽  
Lindsey Shallberg ◽  
Martin Fan ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Immunity ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cross Linking ◽  
Preclinical Models ◽  
T Cell Priming

Targeting of T lymphocytes against egf-receptor+ tumor cells by bispecific monoclonal antibodies: Requirement of CD3 molecule cross-linking for t-cell activation

1993 ◽  
Vol 55 (6) ◽  
pp. 931-937 ◽  
Author(s):  
Silvano Ferrini ◽  
Anna Cambiaggi ◽  
Sabrina Sforzini ◽  
Sabrina Marciano ◽  
Silvana Canevari ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Egf Receptor ◽  
Cross Linking

scholarly journals Evidence for differential intracellular signaling via CD4 and CD8 molecules.

1994 ◽  
Vol 179 (2) ◽  
pp. 727-732 ◽  
Author(s):  
K S Ravichandran ◽  
S J Burakoff
Keyword(s):  
Protein Kinase C ◽  
T Cell ◽  
Protein Kinase ◽  
T Cell Activation ◽  
Intracellular Signaling ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Kinase Assay ◽  
Cross Linking ◽  
Kinase C

Although both the CD4 and CD8 molecules enhance antigen responsiveness mediated by the T cell receptor (TCR), it is not known whether CD4 and CD8 initiate similar or different intracellular signals when they act as coreceptors. To characterize the early signals transmitted by CD4 and CD8, both CD4 and CD8 alpha were expressed in the same murine T cell hybridoma. In the double positive transfectants, CD4 and CD8 associated with equal amounts of p56lck (Lck), and both molecules enhanced interleukin 2 (IL-2) production equivalently when cross-linked with suboptimal levels of anti-TCR antibody. However, in an in vitro kinase assay, cross-linking CD4 initiated fourfold greater kinase activity compared with CD8 cross-linking. In the same assay, when CD4 or CD8 was cross-linked to the TCR, novel phosphorylated proteins were found associated with the TCR/CD4 complex but not with the TCR/CD8 complex. Consistent with this data, antiphosphotyrosine immunoblotting revealed greater tyrosine phosphorylation of intracellular substrates after TCR/CD4 cross-linking compared with TCR/CD8 cross-linking. Additionally, a specific protein kinase C inhibitor (RO318220) inhibited CD8-mediated enhancement of IL-2 production far more effectively than CD4-mediated enhancement. Thus, it appears that CD8 alpha may depend more on a protein kinase C-mediated signaling pathway, whereas CD4 may rely on greater tyrosine kinase activation. Such differential signaling via CD4 and CD8 has implications for thymic ontogeny and T cell activation.

scholarly journals Contact-dependent suppression of CD4 T-cell activation and proliferation by B cells activated through IgD cross-linking

Immunology ◽  
2014 ◽  
Vol 144 (3) ◽  
pp. 444-452
Author(s):  
Lorena Preciado-Llanes ◽  
James B. Wing ◽  
Rachel A. Foster ◽  
Jennifer Carlring ◽  
Andrew Lees ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Cross Linking

scholarly journals Non–T Cell Activation Linker (NTAL)

2002 ◽  
Vol 196 (12) ◽  
pp. 1617-1626 ◽  
Author(s):  
Tomáš Brdička ◽  
Martin Imrich ◽  
Pavla Angelisová ◽  
Naděžda Brdičková ◽  
Ondrej Horváth ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Cross Linking ◽  
Multicomponent Complex ◽  
Transient Elevation

A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non–T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcγ- and Fcε-receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cbl. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non–T cells.

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