Factors contributing to the potency of CD8+T cells

被引:8
作者
Sykulev, Yuri [1 ,2 ]
机构
[1] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Dept Med Oncol, Philadelphia, PA 19107 USA
基金
美国国家卫生研究院;
关键词
CYTOLYTIC ACTIVITY; SERINE ESTERASE; T-CELLS; RECEPTOR; COMPLEXES; BINDING; POLARIZATION; CYTOSKELETON; MECHANISMS; DYNAMICS;
D O I
10.1016/j.it.2023.07.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:693 / 700
页数:8
相关论文
共 52 条
  • [1] ENHANCEMENT OF T-CELL RESPONSIVENESS BY THE LYMPHOCYTE-SPECIFIC TYROSINE PROTEIN-KINASE P56LCK
    ABRAHAM, N
    MICELI, MC
    PARNES, JR
    VEILLETTE, A
    [J]. NATURE, 1991, 350 (6313) : 62 - 66
  • [2] Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies
    Anderson, Kristin G.
    Stromnes, Ingunn M.
    Greenberg, Philip D.
    [J]. CANCER CELL, 2017, 31 (03) : 311 - 325
  • [3] Quantum dot/peptide-MHC biosensors reveal strong CD8-dependent cooperation between self and viral antigens that augment the T cell response
    Anikeeva, Nadia
    Lebedeva, Tatiana
    Clapp, Aaron R.
    Goldman, Ellen R.
    Dustin, Michael L.
    Mattoussi, Hedi
    Sykulev, Yuri
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (45) : 16846 - 16851
  • [4] Efficient killing of tumor cells by CAR-T cells requires greater number of engaged CARs than TCRs
    Anikeeva, Nadia
    Panteleev, Sergey
    Mazzanti, Nicholas W.
    Terai, Mizue
    Sato, Takami
    Sykulev, Yuri
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2021, 297 (03)
  • [5] Extent of MHC Clustering Regulates Selectivity and Effectiveness of T Cell Responses
    Anikeeva, Nadia
    Fischer, Nicholas O.
    Blanchette, Craig D.
    Sykulev, Yuri
    [J]. JOURNAL OF IMMUNOLOGY, 2019, 202 (02) : 591 - 597
  • [6] Evidence that the Density of Self Peptide-MHC Ligands Regulates T-Cell Receptor Signaling
    Anikeeva, Nadia
    Gakamsky, Dimitry
    Scholler, Jorgen
    Sykulev, Yuri
    [J]. PLOS ONE, 2012, 7 (08):
  • [7] Mechanisms controlling granule-mediated cytolytic activity of cytotoxic T lymphocytes
    Anikeeva, Nadia
    Sykulev, Yuri
    [J]. IMMUNOLOGIC RESEARCH, 2011, 51 (2-3) : 183 - 194
  • [8] CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery
    Artyomov, Maxim N.
    Lis, Mieszko
    Devadas, Srinivas
    Davis, Mark M.
    Chakraborty, Arup K.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (39) : 16916 - 16921
  • [9] Kinetics of Early T Cell Receptor Signaling Regulate the Pathway of Lytic Granule Delivery to the Secretory Domain
    Beal, Allison M.
    Anikeeva, Nadia
    Varma, Rajat
    Cameron, Thomas O.
    Vasiliver-Shamis, Gaia
    Norris, Philip J.
    Dustin, Michael L.
    Sykulev, Yuri
    [J]. IMMUNITY, 2009, 31 (04) : 632 - 642
  • [10] Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes
    Bousso, P
    Robey, E
    [J]. NATURE IMMUNOLOGY, 2003, 4 (06) : 579 - 585