T cell activation and clonal expansion is the result of the coordinated functions of the receptors for antigen and interleukin (IL)-2. The protein tyrosine kinase p56lck is critical for the generation of signals emanating from the T cell antigen receptor (TCR) and has also been demonstrated to play a role in IL-2 receptor signaling. We demonstrate that an IL-2–dependent, antigen-specific CD4+ T cell clone is not responsive to anti-TCR induced growth when propagated in IL-2, but remains responsive to both antigen and CD3ε-specific monoclonal antibody. Survival of this IL-2–dependent clone in the absence of IL-2 was supported by overexpression of exogenous Bcl-xL. Culture of this clonal variant in the absence of IL-2 rendered it susceptible to anti-TCR–induced signaling, and correlated with the presence of kinase-active Lck associated with the plasma membrane. The same phenotype is observed in primary, resting CD4+ T cells. Furthermore, the presence of kinase active Lck associated with the plasma membrane correlates with the presence of ZAP 70–pp21ζ complexes in both primary T cells and T cell clones in circumstances of responsive anti-TCR signaling. The results presented demonstrate that IL-2 signal transduction results in the functional uncoupling of the TCR complex through altering the subcellular distribution of kinase-active Lck.
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2 November 1998
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November 02 1998
Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling
Loralee Haughn,
Loralee Haughn
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
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Bernadine Leung,
Bernadine Leung
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
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Lawrence Boise,
Lawrence Boise
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
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André Veillette,
André Veillette
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
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Craig Thompson,
Craig Thompson
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
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Michael Julius
Michael Julius
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
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Loralee Haughn
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
Bernadine Leung
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
Lawrence Boise
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
André Veillette
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
Craig Thompson
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
Michael Julius
From the *Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; the ‡Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Center, Toronto, Ontario, Canada M5G 2M9; the §Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101; the ‖McGill Cancer Centre and the Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and the ¶Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637
Address correspondence to Michael Julius, Arthritis and Immune Disorder Research Centre, Suite 700, 620 University Ave., c/o 610 University Ave., Toronto, Ontario, Canada M5G 2M9. Phone: 416-946-6549; Fax: 416-946-6589; E-mail: [email protected]
L. Haughn was supported by a fellowship from the Cancer Research Society, Inc. B. Leung was supported by a Medical Research Council studentship. A. Veillette is the recipient of an MRC Scientist Award. This work was supported by grants from the Medical Research Council of Canada, the National Cancer Institute, and the National Institutes of Health.
L. Haughn and B. Leung contributed equally to this paper.
Received:
February 17 1998
Revision Received:
July 30 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (9): 1575–1586.
Article history
Received:
February 17 1998
Revision Received:
July 30 1998
Citation
Loralee Haughn, Bernadine Leung, Lawrence Boise, André Veillette, Craig Thompson, Michael Julius; Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling . J Exp Med 2 November 1998; 188 (9): 1575–1586. doi: https://doi.org/10.1084/jem.188.9.1575
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