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The Journal of Immunology, 2006, 177: 976-982.
Copyright © 2006 by The American Association of Immunologists

Generation of T Cell Help through a MHC Class I-Restricted TCR1

Helmut W. H. G. Kessels2,3,*, Koen Schepers2,*, Marly D. van den Boom*, David J. Topham{dagger} and Ton N. M. Schumacher4,*

* Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and {dagger} Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642

CD4+ T cells that are activated by a MHC class II/peptide encounter can induce maturation of APCs and promote cytotoxic CD8+ T cell responses. Unfortunately, the number of well-defined tumor-specific CD4+ T cell epitopes that can be exploited for adoptive immunotherapy is limited. To determine whether Th cell responses can be generated by redirecting CD4+ T cells to MHC class I ligands, we have introduced MHC class I-restricted TCRs into postthymic murine CD4+ T cells and examined CD4+ T cell activation and helper function in vitro and in vivo. These experiments indicate that Ag-specific CD4+ T cell help can be induced by the engagement of MHC class I-restricted TCRs in peripheral CD4+ T cells but that it is highly dependent on the coreceptor function of the CD8beta-chain. The ability to generate Th cell immunity by infusion of MHC class I-restricted Th cells may prove useful for the induction of tumor-specific T cell immunity in cases where MHC class II-associated epitopes are lacking.




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