The development and functions of CD4 T cells expressing a transgenic TCR specific for an MHC-I-restricted tumor antigenic epitope

It has been reported that the ratio of CD4 ⁺ to CD8 ⁺ T cells has no bias in a few class I major histocompatibility complex (MHC-I)-restricted T-cell receptor (TCR)-transgenic mice specific for alloantigens or autoantigens, in which most CD4 T cells express an MHC-I-restricted TCR. In this study, we further showed that more than 50% of CD4 ⁺ T cells in MHC-I-restricted P1A tumor antigen-specific TCR (P1ATCR)-transgenic mice could specifically bind to MHC-I/P1A peptide complex. P1A peptide could stimulate the transgenic CD4 ⁺ T cells to proliferate and secrete both type 1 helper T cell and type 2 helper T cell cytokines. The activated CD4 ⁺ T cells also showed cytotoxicity against P1A-expressing tumor cells. The analysis of TCR α-chains showed that these CD4 ⁺ T cells were selected by co-expressing endogenous TCRs. Our results show that CD4 ⁺ T cells from P1ATCR transgenic mice co-expressed an MHC-I-restricted transgenic TCR and another rearranged endogenous TCRs, both of which were functional.