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The Journal of Immunology, 2008, 181, 6002 -6009
Copyright © 2008 by The American Association of Immunologists, Inc.

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TCR Complex-Activated CD8 Adhesion Function by Human T Cells1

Jay C. Varghese and Kevin P. Kane2

Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada

The CD8 receptor plays a central role in the recognition and elimination of virally infected and malignant cells by cytolytic CD8+ T cells. In conjunction with the TCR, the CD8 coreceptor binds Ag-specific class I MHC (MHC-I) molecules expressed by target cells, initiating signaling events that result in T cell activation. Whether CD8 can further function as an adhesion molecule for non-Ag MHC-I is currently unclear in humans. In this study, we show that in human CD8+ T cells, TCR complex signaling activates CD8 adhesion molecule function, resulting in a CD8 interaction with MHC-I that is sufficient to maintain firm T cell adhesion under shear conditions. Secondly, we found that while CD8 adhesive function was triggered by TCR complex activation in differentiated cells, including in vitro generated CTL and ex vivo effector/memory phenotype CD8+ T cells, naive CD8+ T cells were incapable of activated CD8 adhesion. Lastly, we examine the kinetics of, and signaling for, activated CD8 adhesion in humans and identify notable differences from the equivalent CD8 function in mouse. Activated CD8 adhesion induced by TCR signaling may contribute to the more rapid and robust elimination of pathogen-infected cells by differentiated CD8+ T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by grants from the Canadian Institutes of Health Research (MOP 81298) (to K.P.K.) and the Canadian Network for Vaccines and Immunotherapeutics (to K.P.K.). K.P.K. is an Alberta Heritage Foundation for Medical Research Scientist.

2 Address correspondence and reprint requests to Dr. Kevin P. Kane, Department of Medical Microbiology and Immunology, 6-60 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2. E-mail address: kevin.kane{at}ualberta.ca

3 Abbreviations used in this paper: MHC-I, MHC class I; RCF, relative centrifugal force; PKC, protein kinase C.







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