Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein.
Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein.
复制标题
DOI：
10.4049/jimmunol.1102541
复制
发表时间：
2012-02-01
期刊：
影响因子：
--
通讯作者：
Idoyaga J
中科院分区：
文献类型：
--
作者：
Hemmi H;Zaidi N;Wang B;Matos I;Fiorese C;Lubkin A;Zbytnuik L;Suda K;Zhang K;Noda M;Kaisho T;Steinman RM;Idoyaga J
Trem受体家族成员（髓样细胞上表达的触发受体）微调炎症反应。我们先前鉴定了这些受体之一，称为Trem-like 4（Treml 4），主要在脾脏中表达，并通过CD 8 α+ DC和巨噬细胞以高水平表达。与其他Trem家族成员一样，Treml 4具有免疫球蛋白样胞外域和与衔接子DAP 12缔合的短胞质尾区。为了遵循Treml 4-Fc融合蛋白结合坏死细胞的初步结果，我们现在产生敲除小鼠以评估Treml 4在体内摄取和呈递死亡细胞中的作用。Treml 4表达的丧失并不损害CD 8 α+ DC对垂死细胞的摄取或细胞相关抗原向CD 8 + T细胞的交叉呈递，这表明Treml 4与体内其他受体之间存在重叠功能。为了进一步研究Treml 4功能，我们利用新产生的针对Treml 4的mAb，并将其重链工程化以表达3种不同的抗原，即，卵清蛋白、HIV GAGp 24和乳腺癌蛋白HER 2的细胞外结构域。针对Trem 14的卵清蛋白在体内有效地呈递给⑶ 8+和⑶ 4 + T细胞。与成熟刺激物一起沿着给予的抗Trem 14-GAGp 24 mAb诱导了在Trem 14敲除小鼠中未观察到的Th 1抗原特异性应答。此外，使用抗Trem 14 mAb的HER 2靶向引起组合的CD 4+和CD 8 + T细胞免疫，并且两种T细胞都参与对可移植肿瘤的抗性。因此，Treml 4参与体内抗原呈递，并且用抗Treml 4抗体靶向抗原增强了原本幼稚小鼠的免疫。
Members of the Trem receptor family (Triggering receptor expressed on myeloid cells) fine-tune inflammatory responses. We previously identified one of these receptors, called Trem-like 4 (Treml4), expressed mainly in the spleen, and at high levels by CD8α+ DCs and macrophages. Like other Trem family members, Treml4 has an immunoglobulin-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow our initial results that Treml4-Fc fusion proteins bind necrotic cells, we now generated a knock out mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression did not impair uptake of dying cells by CD8α+ DCs or cross-presentation of cell-associated antigen to CD8+ T cells, suggesting overlapping function between Treml4 and other receptors in vivo. To further investigate Treml4 function, we took advantage of a newly generated mAb against Treml4, and engineered its heavy chain to express 3 different antigens, i.e., ovalbumin, HIV GAGp24 and the extracellular domain of the breast cancer protein HER2. Ovalbumin directed to Treml4 was efficiently presented to CD8+ and CD4+ T cells in vivo. Anti-Treml4-GAGp24 mAbs, given along with a maturation stimulus, induced Th1 antigen-specific responses which were not observed in Treml4 knock out mice. Also, HER2 targeting using anti-Treml4 mAbs elicited combined CD4+ and CD8+ T cell immunity, and both T cells participated in resistance to a transplantable tumor. Therefore, Treml4 participates in antigen presentation in vivo, and targeting antigens with anti-Treml4 antibodies enhances immunization of otherwise naïve mice.
登录
查看更多内容
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
4.4
作者：
Hamerman, Jessica A.;Jarjoura, Vessica R.;Lanier, Lewis L.
通讯作者：
Lanier, Lewis L.
DOI：
10.1073/pnas.0812247106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Idoyaga, Juliana;Suda, Nao;Steinman, Ralph M.
通讯作者：
Steinman, Ralph M.
影响因子：
30.8
作者：
Paloneva, J;Kestilä, M;Peltonen, L
通讯作者：
Peltonen, L
CD8α(+)树突状细胞负责诱导外周组织相关抗原的自身耐受。
影响因子：
15.3
作者：
Belz, Gabrielle T;Behrens, Georg M N;Smith, Chris M;Miller, Jacques F A P;Jones, Claerwen;Lejon, Kristina;Fathman, C Garrison;Mueller, Scott N;Shortman, Ken;Carbone, Francis R;Heath, William R
通讯作者：
Heath, William R