The impact of TCR-binding properties and antigen presentation format on T cell responsiveness.
The impact of TCR-binding properties and antigen presentation format on T cell responsiveness.
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DOI：
10.4049/jimmunol.0900054
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Kranz DM
中科院分区：
文献类型：
--
作者：
Chervin AS;Stone JD;Holler PD;Bai A;Chen J;Eisen HN;Kranz DM
TCR与同源肽-MHC（pepMHC）配体的相互作用通常是低亲和力的。这一特征，加上对CD 8/CD 4参与的要求，使得很难剖析TCR结合参数和T细胞活化之间的关系。当比较不同的pepMHC时，解释更加复杂，因为这些pepMHC在稳定性上可能差异很大。为了研究TCR结合特性和T细胞应答之间的关系，在这项研究中，我们表征了由一组TCR介导的相互作用和活性，这些TCR与相同的pepMHC结合差异很大。可溶性TCR的单价结合通过表面等离子体共振表征，并且测试表达这些TCR（有或没有CD 8共表达）的T细胞杂交瘤与pepMHC的单体和寡聚体形式的结合以及随后的应答（IL-2释放）。在不存在CD 8（KD = 600 nM）的情况下引发该应答的结合阈值在完全活性和无活性之间表现出相对尖锐的截止，与APC上对pepMHC的开关样应答一致。然而，当pepMHC被固定（板结合）时，具有最低亲和力TCR的T细胞（例如，KD = 30 μM）应答，即使在不存在CD 8的情况下，也表明这些TCR具有信号传导能力。令人惊讶的是，即使表达高亲和力（KD = 16 nM）TCR沿着CD 8的细胞也对溶液中的寡聚体无反应。研究结果表明，为了驱动下游T细胞反应，pepMHC必须以支持形成适当的超分子簇的形式呈现。
TCR interactions with cognate peptide-MHC (pepMHC) ligands are generally low affinity. This feature, together with the requirement for CD8/CD4 participation, has made it difficult to dissect relationships between TCR-binding parameters and T cell activation. Interpretations are further complicated when comparing different pepMHC, because these can vary greatly in stability. To examine the relationships between TCR-binding properties and T cell responses, in this study we characterized the interactions and activities mediated by a panel of TCRs that differed widely in their binding to the same pepMHC. Monovalent binding of soluble TCR was characterized by surface plasmon resonance, and T cell hybridomas that expressed these TCR, with or without CD8 coexpression, were tested for their binding of monomeric and oligomeric forms of the pepMHC and for subsequent responses (IL-2 release). The binding threshold for eliciting this response in the absence of CD8 (KD = 600 nM) exhibited a relatively sharp cutoff between full activity and no activity, consistent with a switchlike response to pepMHC on APCs. However, when the pepMHC was immobilized (plate bound), T cells with the lowest affinity TCRs (e.g., KD = 30 μM) responded, even in the absence of CD8, indicating that these TCR are signaling competent. Surprisingly, even cells that expressed high-affinity (KD = 16 nM) TCRs along with CD8 were unresponsive to oligomers in solution. The findings suggest that to drive downstream T cell responses, pepMHC must be presented in a form that supports formation of appropriate supramolecular clusters.
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DOI：
10.1084/jem.191.2.335
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Daniels MA;Jameson SC
通讯作者：
Jameson SC
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：
32.4
作者：
Cochran, JR;Cameron, TO;Stern, LJ
通讯作者：
Stern, LJ
影响因子：
32.4
作者：
Boniface, JJ;Rabinowitz, JD;Davis, MM
通讯作者：
Davis, MM
DOI：
10.1073/pnas.94.25.13838
发表时间：
1997-12-09
影响因子：
11.1
作者：
Garcia, KC;Tallquist, MD;Teyton, L
通讯作者：
Teyton, L