Extracellular Domains of CD8α and CD8ß Subunits Are Sufficient for HLA Class I Restricted Helper Functions of TCR-Engineered CD4+ T Cells

By gene transfer of HLA-class I restricted T-cell receptors (TCRs) (HLA-I-TCR) into CD8 + as well as CD4 + T-cells, both effector T-cells as well as helper T-cells can be generated. Since most HLA-I-TCRs function best in the presence of the CD8 co-receptor, the CD8αß molecule has to be co-transferred into the CD4 + T-cells to engineer optimal helper T-cells. In this study, we set out to determine the minimal part of CD8αβ needed for optimal co-receptor function in HLA-I-TCR transduced CD4 + T-cells. For this purpose, we transduced human peripheral blood derived CD4 + T-cells with several HLA-class I restricted TCRs either with or without co-transfer of different CD8 subunits. We demonstrate that the co-transduced CD8αβ co-receptor in HLA-I-TCR transduced CD4 + T-cells behaves as an adhesion molecule, since for optimal antigen-specific HLA class I restricted CD4 + T-cell reactivity the extracellular domains of the CD8α and ß subunits are sufficient.