Nature Immunology
3, 251 - 258 (2002)
Published online: 11 February 2002; | doi:10.1038/ni765
Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signalingEric Sebzda1, Madelon Bracke2, Tamara Tugal1, Nancy Hogg2
& Doreen Ann Cantrell11
Lymphocyte Activation Laboratory, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. 2
Leukocyte Adhesion Laboratory, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Correspondence should be addressed to Doreen Ann Cantrell doreen.cantrell@cancer.org.ukT cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is reported to antagonize Ras signaling and induces T cell anergy. To address its role in vivo, we generated transgenic mice that constitutively expressed active Rap1A within the T cell lineage. We found that active Rap1A did not interfere with the Ras signaling pathway or antagonize T cell activation. Instead of anergy, the T lymphocytes that constitutively expressed active Rap1A showed enhanced TCR-mediated responses, both in thymocytes and mature T cells. In addition, Rap1A activation was sufficient to induce strong activation of the  1 and 2 integrins via an avidity-modulation mechanism. This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation.
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