Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling

被引：86

作者：

Jun, JE

Goodnow, CC ^{[1
]}

机构：

[1] Australian Natl Univ, John Curtin Sch Med Res, Genet Lab, Australian Canc Res Fdn, Canberra, ACT 2601, Australia

[2] Australian Natl Univ, John Curtin Sch Med Res, Med Genome Ctr, Canberra, ACT 2601, Australia

来源：

NATURE IMMUNOLOGY | 2003年 / 4卷 / 11期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ni1001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Lymphocyte antigen receptors are responsible for inducing the opposite responses of immunity or tolerance. How the correct polarity of antigen receptor signaling is encoded has been an enduring enigma. Here we summarize recent advances defining key scaffolding molecules, CARMA1 (also known as CARD11) and the Cbl family of ubiquitin ligases, required for either immunogenic or tolerogenic signaling by antigen receptors. These scaffolding proteins may determine the polarity of response to antigen by promoting assembly around antigen receptors of competing multiprotein signal complexes: immunosomes versus tolerosomes. Each of the factors that influence immunogenicity or tolerogenicity-stage of lymphocyte differentiation, concurrent engagement of inhibitory or costimulatory receptors, extent of receptor crosslinking, and prior antigen experience-may be integrated in lymphocytes through their capacity to influence the probability of assembling immunosomes versus tolerosomes.

引用

页码：1057 / 1064

页数：8

共 113 条

[71]

Mondino A, 1996, J IMMUNOL, V157, P2048

[72] c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation [J].

Naramura, M ;

Jang, IK ;

Kole, H ;

Huang, F ;

Haines, D ;

Gu, H .

NATURE IMMUNOLOGY, 2002, 3 (12) :1192-1199

[73] Altered thymic positive selection and intracellular signals in Cb1-deficient mice [J].

Naramura, M ;

Kole, HK ;

Hu, RJ ;

Gu, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) :15547-15552

[74] ESSENTIAL ROLE FOR ZAP-70 IN BOTH POSITIVE AND NEGATIVE SELECTION OF THYMOCYTES [J].

NEGISHI, I ;

MOTOYAMA, N ;

NAKAYAMA, K ;

SENJU, S ;

HATAKEYAMA, S ;

ZHANG, Q ;

CHAN, AC ;

LOH, DY .

NATURE, 1995, 376 (6539) :435-438

[75] Mice lacking the CARD of CARMA1 exhibit defective B lymphocyte development and impaired proliferation of their B and T lymphocytes [J].

Newton, K ;

Dixit, VM .

CURRENT BIOLOGY, 2003, 13 (14) :1247-1251

[76]

NOSSAL G. J. V., 1957, AUSTRALIAN JOUR EXPTL BIOL AND MED SCI, V35, P549, DOI 10.1038/icb.1957.57

[77] Signal transduction - Molecular ticket to enter cells [J].

Oved, S ;

Yarden, Y .

NATURE, 2002, 416 (6877) :133-136

[78] NFATc1 and NFATc2 together control both T and B cell activation and differentiation [J].

Peng, SL ;

Gerth, AJ ;

Ranger, AM ;

Glimcher, LH .

IMMUNITY, 2001, 14 (01) :13-20

[79] Lymphocyte lipid rafts: structure and function [J].

Pizzo, P ;

Viola, A .

CURRENT OPINION IN IMMUNOLOGY, 2003, 15 (03) :255-260

[80] CARD11 mediates factor-specific activation of NF-κB by the T cell receptor complex [J].

Pomerantz, JL ;

Denny, EM ;

Baltimore, D .

EMBO JOURNAL, 2002, 21 (19) :5184-5194

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