Generation of T cell help through a MHC class I-Restricted TCR

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 CD8 beta-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.