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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}unibas.ch (E.P.); teixeiropernase{at}missouri.edu (E.T.)

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