Opposite effects of endogenous peptide-MHC class I on T cell activity in the presence and absence of CD8.
Opposite effects of endogenous peptide-MHC class I on T cell activity in the presence and absence of CD8.
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DOI：
10.4049/jimmunol.1003755
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发表时间：
2011-05-01
期刊：
影响因子：
--
通讯作者：
Kranz DM
中科院分区：
文献类型：
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作者：
Stone JD;Aggen DH;Chervin AS;Narayanan S;Schmitt TM;Greenberg PD;Kranz DM
呈递在APC表面上的非刺激性或内源性pepMHC，单独或与激动剂pepMHC一起，在T细胞选择和活化中发挥各种作用。为了更详细地检查这些性质，在这里，我们探索了TCR和pepMHC配体的几种模型系统，其具有足够的亲和力以在不存在CD 8的情况下被激活。TCR对激动剂和非刺激性配体具有一系列亲和力，并且受到具有不同性质的I类MHC等位基因的限制。我们观察到来自TCR：pepMHC相互作用的CD 8非依赖性拮抗作用具有非常低的亲和力（例如KD = 300μM）。此外，APC上的内源性pep/Ld复合物甚至通过强激动剂QL 9/Ld拮抗共受体（CD 8）阴性2C T细胞的活化。相比之下，分别受Kb和Db限制的TCR m33和3D-PYY在不存在CD 8的情况下不显示内源性pepMHC的拮抗迹象。这似乎不是TCR被拮抗能力的固有差异，因为改变的肽配体可以拮抗每种TCR。在CD 8的存在下，内源性pepMHC配体在某些情况下充当共激动剂。这些结果表明内源性pepMHC分子在T细胞中表现出复杂的行为，导致活性降低（例如在低共受体水平的情况下）或活性增强（例如在共受体存在下）。该行为可能受到不同TCR识别内源性pepMHC的能力的影响，但也可能受到呈递MHC等位基因的固有性质的影响。
Non-stimulatory or endogenous pepMHC presented on the surface of APCs, either alone or alongside agonist pepMHC, play various roles in T cell selection and activation. To examine these properties in more detail, here we explored several model systems of TCR and pepMHC ligands with sufficient affinity to be activated in the absence of CD8. The TCRs had a range of affinities for agonist and non-stimulatory ligands, and were restricted by class I MHC alleles with different properties. We observed CD8-independent antagonism from TCR:pepMHC interactions with very low affinities (e.g. KD = 300μM). In addition, endogenous pep/Ld complexes on APCs antagonized activation of co-receptor (CD8)-negative 2C T cells even by the strong agonist QL9/Ld. In contrast, TCRs m33 and 3D-PYY, restricted by Kb and Db, respectively, did not show signs of antagonism by endogenous pepMHC in the absence of CD8. This did not appear to be an inherent difference in the ability of the TCRs to be antagonized, as altered peptide ligands could antagonize each TCR. In the presence of CD8, endogenous pepMHC ligands acted in some cases as co-agonists. These results show that endogenous pepMHC molecules exhibit complex behavior in T cells, leading to either reduced activity (e.g. in cases of low co-receptor levels) or enhanced activity (e.g. in presence of co-receptor). The behavior may be influenced by the ability of different TCRs to recognize endogenous pepMHC, but also perhaps by the inherent properties of the presenting MHC allele.
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影响因子：
64.8
作者：
Daniels, Mark A.;Teixeiro, Emma;Palmer, Ed
通讯作者：
Palmer, Ed
影响因子：
64.8
作者：
Alam, SM;Travers, PJ;Gascoigne, NRJ
通讯作者：
Gascoigne, NRJ
影响因子：
4.4
作者：
Jones, Lindsay L.;Colf, Leremy A.;Kranz, David M.
通讯作者：
Kranz, David M.
部分磷酸化的T细胞受体Zeta分子可以抑制T细胞活化。
DOI：
10.1084/jem.190.11.1627
发表时间：
1999-12-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kersh EN;Kersh GJ;Allen PM
通讯作者：
Allen PM
影响因子：
30.5
作者：
通讯作者：
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