Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation

G. Pantaleo, D. Olive, A. Poggi, T. Pozzan, L. Moretta, A. Moretta

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Abstract

We investigated the mechanism involved in T cell unresponsiveness that follows the monoclonal antibody-induced surface modulation of the CD3-TCR complex. We determined whether modulation of CD3-TCR affected the early metabolic steps such a [Ca2+](i) rise and InsP3 formation. A strong inhibition of the increase on [Ca2+](i) mediated by either anti-TCR or anti-CD2 mAbs was detected. In contrast, surface modulation of CD2 molecules did not prevent the [Ca2+](i) increase induced by anti-TCR mAb. Similarly, InsP3 increase was strongly reduced only after modulation of CD3-TCR complex (but not of CD2 molecules). Therefore, it appears that surface modulation of CD3-TCR complex causes T cell refractoriness by inhibiting the very early metabolic events that follow receptor-ligand interactions.

Original languageEnglish
Pages (from-to)619-624
Number of pages6
JournalJournal of Experimental Medicine
Volume166
Issue number2
Publication statusPublished - 1987

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T-Cell Antigen Receptor-CD3 Complex
T-Cell Antigen Receptor
T-Lymphocytes
Antibodies
Monoclonal Antibodies
Ligands

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation",
abstract = "We investigated the mechanism involved in T cell unresponsiveness that follows the monoclonal antibody-induced surface modulation of the CD3-TCR complex. We determined whether modulation of CD3-TCR affected the early metabolic steps such a [Ca2+](i) rise and InsP3 formation. A strong inhibition of the increase on [Ca2+](i) mediated by either anti-TCR or anti-CD2 mAbs was detected. In contrast, surface modulation of CD2 molecules did not prevent the [Ca2+](i) increase induced by anti-TCR mAb. Similarly, InsP3 increase was strongly reduced only after modulation of CD3-TCR complex (but not of CD2 molecules). Therefore, it appears that surface modulation of CD3-TCR complex causes T cell refractoriness by inhibiting the very early metabolic events that follow receptor-ligand interactions.",
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T1 - Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation

AU - Pantaleo, G.

AU - Olive, D.

AU - Poggi, A.

AU - Pozzan, T.

AU - Moretta, L.

AU - Moretta, A.

PY - 1987

Y1 - 1987

N2 - We investigated the mechanism involved in T cell unresponsiveness that follows the monoclonal antibody-induced surface modulation of the CD3-TCR complex. We determined whether modulation of CD3-TCR affected the early metabolic steps such a [Ca2+](i) rise and InsP3 formation. A strong inhibition of the increase on [Ca2+](i) mediated by either anti-TCR or anti-CD2 mAbs was detected. In contrast, surface modulation of CD2 molecules did not prevent the [Ca2+](i) increase induced by anti-TCR mAb. Similarly, InsP3 increase was strongly reduced only after modulation of CD3-TCR complex (but not of CD2 molecules). Therefore, it appears that surface modulation of CD3-TCR complex causes T cell refractoriness by inhibiting the very early metabolic events that follow receptor-ligand interactions.

AB - We investigated the mechanism involved in T cell unresponsiveness that follows the monoclonal antibody-induced surface modulation of the CD3-TCR complex. We determined whether modulation of CD3-TCR affected the early metabolic steps such a [Ca2+](i) rise and InsP3 formation. A strong inhibition of the increase on [Ca2+](i) mediated by either anti-TCR or anti-CD2 mAbs was detected. In contrast, surface modulation of CD2 molecules did not prevent the [Ca2+](i) increase induced by anti-TCR mAb. Similarly, InsP3 increase was strongly reduced only after modulation of CD3-TCR complex (but not of CD2 molecules). Therefore, it appears that surface modulation of CD3-TCR complex causes T cell refractoriness by inhibiting the very early metabolic events that follow receptor-ligand interactions.

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