Identification of different functions of CD8+ T cell subpopulations by a novel monoclonal antibody

Abstract

The explicit identification of CD8⁺ T cell subpopulation is important for deciphering the role of CD8⁺ T cells for protecting our body against invading pathogens and cancer. Our generated monoclonal antibody (mAb), named FE-1H10, recognized two novel subpopulations of peripheral blood CD8⁺ T cells, FE-1H10⁺ and FE-1H10⁻ CD8⁺ T cells. The molecule recognized by mAb FE-1H10 (FE-1H10 molecules) had a higher distribution on effector memory CD8⁺ T cell subsets. The functions of FE-1H10⁻ and FE-1H10⁺ CD8⁺ T cells were investigated. T cell proliferation assays revealed that FE-1H10⁻ CD8⁺ T cells exhibited a higher proliferation rate than FE-1H10⁺ CD8⁺ T cells, whereas FE-1H10⁺ CD8⁺ T cells produced higher levels of IFN-γ and TNF-α than FE-1H10⁻ CD8⁺ T cells. In T cell cytotoxicity assays, FE-1H10⁺ CD8⁺ T cells were able to kill target cells better than FE-1H10⁻ CD8⁺ T cells. RNA-sequencing analysis confirmed that these subpopulations were distinct: FE-1H10⁺ CD8⁺ T cells have higher expression of genes involved in effector functions (IFNG, TNF, GZMB, PRF1, GNLY, FASL, CX3CR1) while FE-1H10⁻ CD8⁺ T cells have greater expression of genes related to memory CD8⁺ T cell populations (CCR7, SELL, TCF7, CD40LG). The results suggested that mAb FE-1H10 identifies two novel distinctive CD8⁺ T cell subpopulations. The FE-1H10⁺ CD8⁺ T cells carried a superior functionality in response to tumour cells. The uncover of these novel CD8⁺ T cell subpopulations may be the basis knowledge of an optional immunotherapy for the selection of potential CD8⁺ T cells in cancer treatment.