Factors contributing to the potency of CD8+ T cells |
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| Institution: | 1. Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA;2. Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA;1. Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA;2. Department of Pediatrics and Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53705, USA;1. Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg;2. Immunology and Genetics, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg;3. Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, Denmark;1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;2. Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA;2. Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA;3. Broad Institute of MIT and Harvard, Cambridge, MA, USA;4. Evergrande Center for Immunological Diseases, Harvard Medical School, Boston, MA, USA;5. Brigham and Women’s Hospital, Boston, MA, USA;1. i3S – Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal;2. Graduate Program in Areas of Applied and Basic Biology (GABBA), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal;3. School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal;4. Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;1. Cell Death and Inflammation Unit, Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, 9052 Ghent, Belgium;2. Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium |
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| Abstract: | CD8+ cytotoxic T lymphocytes (CTLs) play a crucial role in targeting virus-infected and cancer cells. Although other cytotoxic lymphocytes such as CD4+ T and natural killer (NK) cells, as well as chimeric antigen receptor (CAR)-T cells, can also identify and destroy aberrant cells, they seem to be significantly less potent based on available experimental data. Here, I contemplate the molecular mechanisms controlling the sensitivity and kinetics of granule-mediated CD8+ T cell cytolytic responses. I posit that the clustering of MHC-I molecules and T cell receptors (TCRs) on the cell surface, as well as the contribution of the CD8 co-receptor, are major factors driving exceptionally potent cytolytic responses. I also contend that CD8+ T cells with known specificity and engineered TCR-T cells might be among the most efficient cytolytic effectors for treating patients suffering from viral infections or cancer. |
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