Kinetics of Early T Cell Receptor Signaling Regulate the Pathway of Lytic Granule Delivery to the Secretory Domain

被引：101

作者：

Beal, Allison M. ^{[1
,2
]}

Anikeeva, Nadia ^{[1
,2
]}

Varma, Rajat ^{[3
]}

Cameron, Thomas O. ^{[3
]}

Vasiliver-Shamis, Gaia ^{[3
]}

Norris, Philip J. ^{[4
,5
,6
]}

Dustin, Michael L. ^{[3
]}

Sykulev, Yuri ^{[1
,2
]}

机构：

[1] Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Kimmel Canc Inst, Philadelphia, PA 19107 USA

[3] NYU, Sch Med, Helen L & Martin S Kimmel Ctr Biol & Med, Skirball Inst Biomol Med, New York, NY 10016 USA

[4] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94118 USA

[5] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94118 USA

[6] Univ Calif San Francisco, Dept Med, San Francisco, CA 94118 USA

来源：

IMMUNITY | 2009年 / 31卷 / 04期

关键词：

MICROTUBULE-ORGANIZING CENTER; SUPRAMOLECULAR ACTIVATION CLUSTERS; IMMUNOLOGICAL SYNAPSE; EFFECTOR FUNCTIONS; TARGET-CELL; CLASS-I; POLARIZATION; LYMPHOCYTES; RECRUITMENT; PROTEIN;

D O I：

10.1016/j.immuni.2009.09.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Cytolytic granules mediate killing of virus-infected cells by cytotoxic T lymphocytes. We show here that the granules can take long or short paths to the secretory domain. Both paths utilized the same intracellular molecular events, which have different spatial and temporal arrangements and are regulated by the kinetics of Ca2+-mediated signaling. Rapid signaling caused swift granule concentration near the microtubule-organizing center (MTOC) and subsequent delivery by the polarized MTOC directly to the secretory domain-the shortest path. Indolent signaling led to late recruitment of granules that moved along microtubules to the periphery of the synapse and then moved tangentially to fuse at the outer edge of the secretory domain-a longer path. The short pathway is associated with faster granule release and more efficient killing than the long pathway. Thus, the kinetics of early signaling regulates the quality of the T cell cytolytic response.

引用

页码：632 / 642

页数：11

共 44 条

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Distinct role of lymphocyte fuinction-associated antigen-1 in mediating effective cytolytic activity by cytotoxic T lymphocytes [J].