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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. [ABSTRACT FROM AUTHOR]

CD99 was demonstrated to be a potential target for antibody therapy on T-acute lymphoblastic leukemia (T-ALL). The ligation of CD99 by certain monoclonal antibodies (mAbs) induced T-ALL apoptosis. However, the molecular basis contributing to the apoptosis of T-ALL upon anti-CD99 mAb engagement remains elusive. In this study, using our generated anti-CD99 mAb clone MT99/3 (mAb MT99/3), mAb MT99/3 engagement strongly induced apoptosis of T-ALL cell lines, but not in non-malignant peripheral blood cells. By transcriptome analysis, upon mAb MT99/3 ligation, 13 apoptosis-related genes, including FOS, TNF, FASLG, BCL2A1, JUNB, SOCS1, IL27RA, PTPN6, PDGFA, NR4A1, SGK1, LPAR5 and LTB, were significantly upregulated. The epitope of CD99 recognized by mAb MT99/3 was then identified as the VDGENDDPRPP at residues 60–70 of CD99, which has never been reported. To the best of our knowledge, this is the first transcriptome data conducted in T-ALL with anti-CD99 mAb engagement. These findings provide new insights into CD99 implicated in the apoptosis of T-ALL. The identification of a new epitope and apoptosis-related genes that relate to the induction of apoptosis by mAb MT99/3 may serve as a new therapeutic target for T-ALL. The anti-CD99 mAb clone MT99/3 might be a candidate for further development of a therapeutic antibody for T-ALL therapy. [ABSTRACT FROM AUTHOR]

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., (© 2024 John Wiley & Sons Ltd.)