CD28 plays a critical role in the segregation of PKCθ within the immunologic synapse

被引:125
作者
Huang, JY
Lo, PF
Zal, T
Gascoigne, NRJ
Smith, BA
Levin, SD
Grey, HM
机构
[1] La Jolla Inst Allergy & Immunol, Div Immunochem, San Diego, CA 92121 USA
[2] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Microscopy Core Facil, La Jolla, CA 92037 USA
[4] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
关键词
D O I
10.1073/pnas.142298399
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The signaling pathways that lead to the localization of cellular protein to the area of interaction between T cell and antigen-presenting cell and the mechanism by which these molecules are further sorted to the peripheral supramolecular activation cluster or central supramolecular activation cluster regions of the immunologic synapse are poorly understood. In this study, we investigated the functional involvement of CD28 costimulation in the T cell receptor (TCR)-mediated immunologic synapse formation with respect to protein kinase C (PKC)theta localization. We showed that CD3 crosslinking alone was sufficient to induce PKCtheta capping in naive CD4(+) T cells. Studies with pharmacologic inhibitors and knockout mice showed that the TCR-derived signaling that drives PKCtheta membrane. translocation requires the Src family kinase, Lck, but not Fyn. In addition, a time course study of the persistence of T cell molecules to the immunologic synapse indicated that PKCtheta, unlike TCR, persisted in the synapse for at least 4 h, a time that is sufficient for commitment of a T cell to cell division. Finally, by using TCR-transgenic T cells from either wild-type or CD28-deficient mice, we showed that CD28 expression was required for the formation of the mature immunologic synapse, because antigen stimulation of CD28- T cells led to a diffuse pattern of localization of PKCtheta and lymphocyte function-associated antigen-1 in the immunologic synapse, in contrast to the central supramolecular activation cluster localization of PKCtheta in CD28(+) T cells.
引用
收藏
页码:9369 / 9373
页数:5
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