The receptor Ly108 functions as a SAP adaptor-dependent on-off switch for T cell help to B cells and NKT cell development.
The receptor Ly108 functions as a SAP adaptor-dependent on-off switch for T cell help to B cells and NKT cell development.
复制标题
受体LY108充当SAP适应器依赖性的开关开关，可帮助B细胞和NKT细胞发育。
DOI：
10.1016/j.immuni.2012.05.016
复制
发表时间：
2012-06-29
期刊：
影响因子：
32.4
通讯作者：
Crotty S
中科院分区：
文献类型：
--
作者：
Kageyama R;Cannons JL;Zhao F;Yusuf I;Lao C;Locci M;Schwartzberg PL;Crotty S
由于缺乏T细胞对B细胞的帮助，缺乏衔接蛋白SAP（Sh 2d 1a）的人和小鼠在体液免疫方面存在重大缺陷。SAP在这一过程中的作用尚未完全了解。我们发现，CD 4 + T细胞中受体Ly 108（Slamf 6）的缺失逆转了Sh 2d 1a −/−表型，消除了SAP对生发中心的需求。Ly 108的这种强有力的负信号传导需要免疫酪氨酸开关基序（ITSM）和SHP-1募集，导致T：B突触处的大量SHP-1，限制T：B粘附。Ly 108负信号不仅在CD 4 + T细胞中很重要，因为我们发现NKT细胞分化在Slamf 6 −/− Sh 2d 1a −/−小鼠中基本恢复。SAP调节T细胞中的正信号和负信号的能力可以解释SAP缺陷的严重性，并强调SAP和SHP-1竞争Ly 108 ITSM结合作为T细胞帮助B细胞的大小的变阻器的重要性。
Humans and mice deficient in the adaptor protein SAP (Sh2d1a) have a major defect in humoral immunity, due to lack of T cell help for B cells. The role of SAP in this process is incompletely understood. We found that deletion of receptor Ly108 (Slamf6) in CD4+ T cells reversed the Sh2d1a−/− phenotype, eliminating the SAP requirement for germinal centers. This potent negative signaling by Ly108 required immunotyrosine switch motifs (ITSMs) and SHP-1 recruitment, resulting in high amounts of SHP-1 at the T:B synapse, limiting T:B adhesion. Ly108 negative signaling was not only important in CD4+ T cells, as we found that NKT cell differentiation was substantially restored in Slamf6−/−Sh2d1a−/− mice. The ability of SAP to regulate both positive and negative signals in T cells can explain the severity of SAP-deficiency and highlights the importance of SAP and SHP-1 competition for Ly108 ITSM binding as a rheostat for the magnitude of T cell help to B cells.
登录
查看更多内容
影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
64.8
作者：
Crotty, S;Kersh, EN;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
32.4
作者：
Deenick EK;Chan A;Ma CS;Gatto D;Schwartzberg PL;Brink R;Tangye SG
通讯作者：
Tangye SG
DOI：
10.1084/jem.20052097
发表时间：
2006-06-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cannons JL;Yu LJ;Jankovic D;Crotty S;Horai R;Kirby M;Anderson S;Cheever AW;Sher A;Schwartzberg PL
通讯作者：
Schwartzberg PL
影响因子：
4.4
作者：
Graham, DB;Bell, MP;McKean, DJ
通讯作者：
McKean, DJ