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Science 323 (5913): 502-505

Copyright © 2009 by the American Association for the Advancement of Science

Different T Cell Receptor Signals Determine CD8+ Memory Versus Effector Development

Emma Teixeiro,1,2{dagger} Mark A. Daniels,1,2* Sara E. Hamilton,3* Adam G. Schrum,1,5 Rafael Bragado,4 Stephen C. Jameson,3 Ed Palmer1{dagger}

Abstract: Following infection, naïve CD8+ T cells bearing pathogen-specific T cell receptors (TCRs) differentiate into a mixed population of short-lived effector and long-lived memory T cells to mediate an adaptive immune response. How the TCR regulates memory T cell development has remained elusive. Using a mutant TCR transgenic model, we found that point mutations in the TCR β transmembrane domain (βTMD) impair the development and function of CD8+ memory T cells without affecting primary effector T cell responses. Mutant T cells are deficient in polarizing the TCR and in organizing the nuclear factor {kappa}B signal at the immunological synapse. Thus, effector and memory states of CD8+ T cells are separable fates, determined by differential TCR signaling.

1 Experimental Transplantation Immunology, Department of Biomedicine, University Hospital-Basel, Hebelstrasse 20, 4031-Basel, Switzerland.
2 Department of Molecular Microbiology and Immunology, University of Missouri, School of Medicine, Center for Cellular and Molecular Immunology, Columbia, MO 65212, USA.
3 Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55454, USA.
4 Department of Immunology, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040-Madrid, Spain.
5 Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905,USA.

* These authors have contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ed.palmer{at} (E.P.); teixeiropernase{at} (E.T.)

Cutting Edge: The Signals for the Generation of T Cell Memory Are Qualitatively Different Depending on TCR Ligand Strength.
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N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T cell memory but not to effector differentiation.
S. Iborra, M. Ramos, D. M. Arana, S. Lazaro, F. Aguilar, E. Santos, D. Lopez, E. Fernandez-Malave, and M. Del Val (2013)
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Signal Integration by Akt Regulates CD8 T Cell Effector and Memory Differentiation.
E. H. Kim, J. A. Sullivan, E. H. Plisch, M. M. Tejera, A. Jatzek, K. Y. Choi, and M. Suresh (2012)
J. Immunol. 188, 4305-4314
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J. Shin, T. F. O'Brien, J. M. Grayson, and X.-P. Zhong (2012)
J. Immunol. 188, 2111-2117
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DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice.
K. L. Randall, S. S.- Y. Chan, C. S. Ma, I. Fung, Y. Mei, M. Yabas, A. Tan, P. D. Arkwright, W. Al Suwairi, S. O. Lugo Reyes, et al. (2011)
J. Exp. Med. 208, 2305-2320
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Physical and Functional Bivalency Observed Among TCR/CD3 Complexes Isolated from Primary T Cells.
A. G. Schrum, D. Gil, L. A. Turka, and E. Palmer (2011)
J. Immunol. 187, 870-878
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Control of Toxoplasma reactivation by rescue of dysfunctional CD8+ T-cell response via PD-1-PDL-1 blockade.
R. Bhadra, J. P. Gigley, L. M. Weiss, and I. A. Khan (2011)
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Strength of TCR-Peptide/MHC Interactions and In Vivo T Cell Responses.
E. Corse, R. A. Gottschalk, and J. P. Allison (2011)
J. Immunol. 186, 5039-5045
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Gads Regulates the Expansion Phase of CD8+ T Cell-Mediated Immunity.
E. Y. Zhang, B. L. Parker, and T. M. Yankee (2011)
J. Immunol. 186, 4579-4589
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Intrinsic IL-21 Signaling Is Critical for CD8 T Cell Survival and Memory Formation in Response to Vaccinia Viral Infection.
P. Novy, X. Huang, W. J. Leonard, and Y. Yang (2011)
J. Immunol. 186, 2729-2738
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T-cell receptor signals direct the composition and function of the memory CD8+ T-cell pool.
J. E. Smith-Garvin, J. C. Burns, M. Gohil, T. Zou, J. S. Kim, J. S. Maltzman, E. J. Wherry, G. A. Koretzky, and M. S. Jordan (2010)
Blood 116, 5548-5559
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Phenotypic Definition of Effector and Memory T-Lymphocyte Subsets in Mice Chronically Infected with Mycobacterium tuberculosis.
M. I. Henao-Tamayo, D. J. Ordway, S. M. Irwin, S. Shang, C. Shanley, and I. M. Orme (2010)
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The {alpha}{beta} T Cell Receptor Is an Anisotropic Mechanosensor.
S. T. Kim, K. Takeuchi, Z.-Y. J. Sun, M. Touma, C. E. Castro, A. Fahmy, M. J. Lang, G. Wagner, and E. L. Reinherz (2009)
J. Biol. Chem. 284, 31028-31037
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S. Feau and S. P. Schoenberger (2009)
Science 323, 466-467
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