Gamma delta T cells recognize haptens and mount a hapten-specific response.
Gamma delta T cells recognize haptens and mount a hapten-specific response.
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DOI：
10.7554/elife.03609
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发表时间：
2014-09-25
期刊：
影响因子：
7.7
通讯作者：
Chien YH
中科院分区：
文献类型：
--
作者：
Zeng X;Meyer C;Huang J;Newell EW;Kidd BA;Wei YL;Chien YH
识别小有机分子和宿主分子化学修饰的能力是适应性免疫系统的基本能力，迄今为止，人们认为适应性免疫系统主要是由B细胞抗原受体介导的。在这里，我们报道了小分子，如合成荧光分子氰氨酸3 （Cy3）和最著名的半抗原之一4-羟基-3-硝基苯基乙酰基（NP），是γδ T细胞抗原，可被特异性γδ tcr直接识别。Cy3偶联物免疫可诱导快速的Cy3特异性γδ T细胞IL-17应答。这些结果扩大了小分子和化学修饰在免疫中的作用，并强调了γδ T细胞作为独特的适应性免疫细胞的作用，它将B细胞样抗原识别能力与T细胞效应功能结合起来。我们的免疫系统对入侵的微生物（如病毒和细菌）做出反应，并试图通过两个不同但相互关联的系统来消除威胁：先天免疫系统和适应性免疫系统。先天免疫系统的细胞在我们的器官和组织中巡逻，努力以快速而普遍的反应识别和消除威胁，这对许多不同的病原体都是相似的。这第一道防线也通过激活适应性免疫系统来升级免疫反应。与先天免疫反应不同，适应性免疫反应的目标是不同大小、形状和化学成分的独特分子——从小的有机分子到大的病原体。适应性免疫系统由三种类型的免疫细胞组成：B细胞、αβ (αβ) T细胞和γδ (γδ) T细胞。这些细胞表面有充当受体的蛋白质；当受体识别并结合外来分子（称为抗原）时，细胞被激活。然后，这会引发一系列事件，帮助清除感染，并帮助免疫细胞对同一病原体的任何未来感染做出快速反应。αβ T细胞和γδ T细胞响应不同的触发，但执行相似的任务，而B细胞执行的任务与T细胞不同。有效的免疫反应通常涉及B细胞和T细胞。适应性免疫系统识别入侵微生物或监测受损或异常细胞的一个重要方法是识别病原体产生的化学物质和宿主分子的化学修饰。虽然B细胞能做到这一点，但αβ T细胞不能。Zeng等人现在发现γδ T细胞也能识别并对这类抗原产生应答。γδ T细胞被证明可以检测一种小的合成荧光染料和一种化学修饰，这种化学修饰在过去80年里被广泛研究用于B细胞反应。根据这些发现，下一个挑战是鉴定识别感染或疾病期间产生的分子或化合物的γδ T细胞，并确定这些细胞在免疫中的作用。DOI: http://dx.doi.org/10.7554/eLife.03609.002
The ability to recognize small organic molecules and chemical modifications of host molecules is an essential capability of the adaptive immune system, which until now was thought to be mediated mainly by B cell antigen receptors. Here we report that small molecules, such as cyanine 3 (Cy3), a synthetic fluorescent molecule, and 4-hydroxy-3-nitrophenylacetyl (NP), one of the most noted haptens, are γδ T cell antigens, recognized directly by specific γδ TCRs. Immunization with Cy3 conjugates induces a rapid Cy3-specific γδ T cell IL-17 response. These results expand the role of small molecules and chemical modifications in immunity and underscore the role of γδ T cells as unique adaptive immune cells that couple B cell-like antigen recognition capability with T cell effector function. DOI: http://dx.doi.org/10.7554/eLife.03609.001 Our immune system responds to invading microbes—such as viruses and bacteria—and tries to eliminate the threat via two distinct but connected systems: the innate and the adaptive immune systems. Cells of the innate immune system patrol our organs and tissues in an effort to identify and eliminate threats with a quick but general response, which is similar for many different pathogens. This first line of defense also escalates the immune response by activating the adaptive immune system. Unlike the innate immune response, the adaptive immune response targets unique molecules of different sizes, shapes and chemical compositions—ranging from small organic molecules to large pathogens. The adaptive immune system consists of three types of immune cells: B cells, alpha beta (αβ) T cells and gamma delta (γδ) T cells. These cells have proteins on their surfaces that function as receptors; when the receptors recognize and bind to a foreign molecule (called antigen), the cell becomes activated. This then triggers a cascade of events that help to clear the infection and help immune cells to rapidly respond to any future infection by the same pathogen. αβ T cells and γδ T cells respond to different triggers, but perform similar tasks—while B cells perform tasks that are different from those of T cells. An effective immune response often involves both B cells and T cells. One important way that the adaptive immune system can identify an invading microbe or monitor for damaged or abnormal cells is by recognizing chemicals produced by pathogen and chemical modifications of host molecules. And while B cells are able to do this, αβ T cells are not. Zeng et al. now show that γδ T cells can also recognize and mount response against this type of antigen. γδ T cells were shown to detect both a small synthetic fluorescent dye, and a chemical modification that has been extensively studied for B cell responses over the last 80 years. Following on from these findings, the next challenge is to identify γδ T cells that recognize molecules or chemical compounds produced during infection or disease, and to define these cells' role in immunity. DOI: http://dx.doi.org/10.7554/eLife.03609.002
DOI：
10.1084/jem.153.6.1445
发表时间：
1981-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sherr DH;Dorf ME
通讯作者：
Dorf ME