Modulation of surface T11 molecules induced by monoclonal antibodies

Analysis of the functional relationship between antigen-dependent and antigen-independent pathways of human T cell activation

A. Moretta, D. Olive, A. Poggi, G. Pantaleo, C. Mawas

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Abstract

Previous data indicated that T lymphocyte activation can be achieved by using a combination of anti-T11 monoclonal antibodies (mAb) directed to the 'T112' and the 'T113' epitopes, respectively. Unlike the T cell activation induced by antibodies directed to the T3 T cell receptor (Ti) complex or to T44 molecules, the anti-T11 mAb-induced cell activation was not accompanied by surface modulation of the T11 antigen. In the present study we show that appropriate stimulatory combinations of anti-T11 mAb are able to induce T11 antigen modulation in a variety of T cells including polyclonal peripheral blood populations, normal as well as leukemic (JA3) T cell clones. The first anti-T11 mAb combination leading to both cell activation and T11 antigen modulation was given by a mAb directed to the T112 epitope and by another mAb recognizing an epitope belonging to the T111 group. The second combination was given by two mAb directed against two different determinants of the T111 group. The ability to induce T11 antigen modulation allowed a more precise analysis of the pathway of T cell activation initiated by T11 molecules and its physical and functional relationship with the other known pathways of T cell activation. T cells following T11 antigen modulation failed to respond to subsequent stimulation with anti-T11 mAb. The refractory period lasted for 48-72 h and the restoration of the responsiveness to anti-T11 mAb coincided with the re-expression of T11 molecules at the cell surface. Modulation of T11 antigen did not affect the surface expression of T3, Ti or T44 molecules, in addition, 'modulated' cells maintained their ability to respond to mAb directed against T3, Ti or T44 molecules. On the contrary, antibody-induced modulation of the T3-Ti receptor complex abrogated both T11- and T44-dependent T cell activation. Finally, antibody-induced modulation of T44 antigen did not inhibit either the T11- or the T3-Ti-dependent pathway of T cell activation. These data indicate that down-regulation of the pathway of T cell activation initiated by T11 molecules can be induced not only by modulation of the antigen receptor complex but also by appropriate mAb to T11 molecules and, presumably, by the natural ligand binding to T11 molecules.

Original languageEnglish
Pages (from-to)1427-1432
Number of pages6
JournalEuropean Journal of Immunology
Volume16
Issue number11
DOIs
Publication statusPublished - 1986

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Monoclonal Antibodies
T-Lymphocytes
Antigens
Epitopes
Antibodies
Thyroid Hormone Receptors
Antigen Receptors
Lymphocyte Activation
T-Cell Antigen Receptor
Down-Regulation
Clone Cells
Ligands
Population

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Modulation of surface T11 molecules induced by monoclonal antibodies: Analysis of the functional relationship between antigen-dependent and antigen-independent pathways of human T cell activation",
abstract = "Previous data indicated that T lymphocyte activation can be achieved by using a combination of anti-T11 monoclonal antibodies (mAb) directed to the 'T112' and the 'T113' epitopes, respectively. Unlike the T cell activation induced by antibodies directed to the T3 T cell receptor (Ti) complex or to T44 molecules, the anti-T11 mAb-induced cell activation was not accompanied by surface modulation of the T11 antigen. In the present study we show that appropriate stimulatory combinations of anti-T11 mAb are able to induce T11 antigen modulation in a variety of T cells including polyclonal peripheral blood populations, normal as well as leukemic (JA3) T cell clones. The first anti-T11 mAb combination leading to both cell activation and T11 antigen modulation was given by a mAb directed to the T112 epitope and by another mAb recognizing an epitope belonging to the T111 group. The second combination was given by two mAb directed against two different determinants of the T111 group. The ability to induce T11 antigen modulation allowed a more precise analysis of the pathway of T cell activation initiated by T11 molecules and its physical and functional relationship with the other known pathways of T cell activation. T cells following T11 antigen modulation failed to respond to subsequent stimulation with anti-T11 mAb. The refractory period lasted for 48-72 h and the restoration of the responsiveness to anti-T11 mAb coincided with the re-expression of T11 molecules at the cell surface. Modulation of T11 antigen did not affect the surface expression of T3, Ti or T44 molecules, in addition, 'modulated' cells maintained their ability to respond to mAb directed against T3, Ti or T44 molecules. On the contrary, antibody-induced modulation of the T3-Ti receptor complex abrogated both T11- and T44-dependent T cell activation. Finally, antibody-induced modulation of T44 antigen did not inhibit either the T11- or the T3-Ti-dependent pathway of T cell activation. These data indicate that down-regulation of the pathway of T cell activation initiated by T11 molecules can be induced not only by modulation of the antigen receptor complex but also by appropriate mAb to T11 molecules and, presumably, by the natural ligand binding to T11 molecules.",
author = "A. Moretta and D. Olive and A. Poggi and G. Pantaleo and C. Mawas",
year = "1986",
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T1 - Modulation of surface T11 molecules induced by monoclonal antibodies

T2 - Analysis of the functional relationship between antigen-dependent and antigen-independent pathways of human T cell activation

AU - Moretta, A.

AU - Olive, D.

AU - Poggi, A.

AU - Pantaleo, G.

AU - Mawas, C.

PY - 1986

Y1 - 1986

N2 - Previous data indicated that T lymphocyte activation can be achieved by using a combination of anti-T11 monoclonal antibodies (mAb) directed to the 'T112' and the 'T113' epitopes, respectively. Unlike the T cell activation induced by antibodies directed to the T3 T cell receptor (Ti) complex or to T44 molecules, the anti-T11 mAb-induced cell activation was not accompanied by surface modulation of the T11 antigen. In the present study we show that appropriate stimulatory combinations of anti-T11 mAb are able to induce T11 antigen modulation in a variety of T cells including polyclonal peripheral blood populations, normal as well as leukemic (JA3) T cell clones. The first anti-T11 mAb combination leading to both cell activation and T11 antigen modulation was given by a mAb directed to the T112 epitope and by another mAb recognizing an epitope belonging to the T111 group. The second combination was given by two mAb directed against two different determinants of the T111 group. The ability to induce T11 antigen modulation allowed a more precise analysis of the pathway of T cell activation initiated by T11 molecules and its physical and functional relationship with the other known pathways of T cell activation. T cells following T11 antigen modulation failed to respond to subsequent stimulation with anti-T11 mAb. The refractory period lasted for 48-72 h and the restoration of the responsiveness to anti-T11 mAb coincided with the re-expression of T11 molecules at the cell surface. Modulation of T11 antigen did not affect the surface expression of T3, Ti or T44 molecules, in addition, 'modulated' cells maintained their ability to respond to mAb directed against T3, Ti or T44 molecules. On the contrary, antibody-induced modulation of the T3-Ti receptor complex abrogated both T11- and T44-dependent T cell activation. Finally, antibody-induced modulation of T44 antigen did not inhibit either the T11- or the T3-Ti-dependent pathway of T cell activation. These data indicate that down-regulation of the pathway of T cell activation initiated by T11 molecules can be induced not only by modulation of the antigen receptor complex but also by appropriate mAb to T11 molecules and, presumably, by the natural ligand binding to T11 molecules.

AB - Previous data indicated that T lymphocyte activation can be achieved by using a combination of anti-T11 monoclonal antibodies (mAb) directed to the 'T112' and the 'T113' epitopes, respectively. Unlike the T cell activation induced by antibodies directed to the T3 T cell receptor (Ti) complex or to T44 molecules, the anti-T11 mAb-induced cell activation was not accompanied by surface modulation of the T11 antigen. In the present study we show that appropriate stimulatory combinations of anti-T11 mAb are able to induce T11 antigen modulation in a variety of T cells including polyclonal peripheral blood populations, normal as well as leukemic (JA3) T cell clones. The first anti-T11 mAb combination leading to both cell activation and T11 antigen modulation was given by a mAb directed to the T112 epitope and by another mAb recognizing an epitope belonging to the T111 group. The second combination was given by two mAb directed against two different determinants of the T111 group. The ability to induce T11 antigen modulation allowed a more precise analysis of the pathway of T cell activation initiated by T11 molecules and its physical and functional relationship with the other known pathways of T cell activation. T cells following T11 antigen modulation failed to respond to subsequent stimulation with anti-T11 mAb. The refractory period lasted for 48-72 h and the restoration of the responsiveness to anti-T11 mAb coincided with the re-expression of T11 molecules at the cell surface. Modulation of T11 antigen did not affect the surface expression of T3, Ti or T44 molecules, in addition, 'modulated' cells maintained their ability to respond to mAb directed against T3, Ti or T44 molecules. On the contrary, antibody-induced modulation of the T3-Ti receptor complex abrogated both T11- and T44-dependent T cell activation. Finally, antibody-induced modulation of T44 antigen did not inhibit either the T11- or the T3-Ti-dependent pathway of T cell activation. These data indicate that down-regulation of the pathway of T cell activation initiated by T11 molecules can be induced not only by modulation of the antigen receptor complex but also by appropriate mAb to T11 molecules and, presumably, by the natural ligand binding to T11 molecules.

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