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H-2 限制:单个受体对 H-2 和外来抗原的独立识别。

H-2 restriction: independent recognition of H-2 and foreign antigen by a single receptor.

作者信息

Siliciano R F, Zacharchuk C M, Shin H S

出版信息

Proc Natl Acad Sci U S A. 1980 Apr;77(4):2192-6. doi: 10.1073/pnas.77.4.2192.

DOI:10.1073/pnas.77.4.2192
PMID:6966404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC348678/
Abstract

We describe two situations in which the recognition of hapten can compensate for the lack of recognition of appropriate H-2 gene products in hapten-specific, H-2 restricted, T lymphocyte-mediated cytolysis. First, we show that although recognition of appropriate H-2 gene products is essential for the lysis of target cells bearing a low hapten density, significant hapten-specific lysis of H-2 inappropriate target cells is observed at high levels of target cell derivatization. Secondly, we show that hapten-conjugated anti-H-2 antibody inhibits cytolysis poorly even though its binding to target cell H-2 antigens is equivalent to that of underivatized antibody. These results suggest that hapten and H-2 are recognized independently and are therefore inconsistent with the altered-self model. Although our data do not exclude the dual-recognition model, we prefer to interpret them within the framework of a single-receptor model in which hapten and H-2 are recognized independently by receptors of identical idiotype on the T cell. We postulate that the affinity of these receptors for the relevant H-2 gene product is low enough so that the T cell is not activated by encounters with normal-self cells expressing that H-2 gene product. However, when self cells express in addition a foreign antigen that can also be recognized by the same receptor, then the force of T cell-target cell interaction may be increased sufficiently to activate T cell effector function.

摘要

我们描述了两种情况,在半抗原特异性、H-2限制性、T淋巴细胞介导的细胞溶解过程中,对半抗原的识别可以弥补对合适H-2基因产物识别的不足。首先,我们发现,虽然识别合适的H-2基因产物对于裂解低半抗原密度的靶细胞至关重要,但在高水平的靶细胞衍生化情况下,可观察到对H-2不匹配的靶细胞有显著的半抗原特异性裂解。其次,我们发现半抗原偶联的抗H-2抗体抑制细胞溶解的能力很差,尽管其与靶细胞H-2抗原的结合与未衍生化抗体相当。这些结果表明,半抗原和H-2是被独立识别的,因此与改变自身模型不一致。虽然我们的数据不排除双重识别模型,但我们更倾向于在单受体模型的框架内解释它们,在该模型中,半抗原和H-2由T细胞上具有相同独特型的受体独立识别。我们推测,这些受体对相关H-2基因产物的亲和力足够低,以至于T细胞不会因与表达该H-2基因产物的正常自身细胞相遇而被激活。然而,当自身细胞另外表达一种也能被同一受体识别的外来抗原时,那么T细胞与靶细胞相互作用的强度可能会增加到足以激活T细胞效应功能的程度。

相似文献

1
H-2 restriction: independent recognition of H-2 and foreign antigen by a single receptor.H-2 限制:单个受体对 H-2 和外来抗原的独立识别。
Proc Natl Acad Sci U S A. 1980 Apr;77(4):2192-6. doi: 10.1073/pnas.77.4.2192.
2
H-2 haplotype specificity of molecular requirements for trinitrophenyl recognition by anti-hapten cytotoxic T lymphocytes.抗半抗原细胞毒性T淋巴细胞识别三硝基苯基的分子要求的H-2单倍型特异性
Cell Immunol. 1981 Feb;58(1):147-55. doi: 10.1016/0008-8749(81)90156-8.
3
Suppression of anti-hapten antibody responses by hapten-specific cytolytic T lymphocytes: role of I-A-associated antigen on target B lymphocytes.半抗原特异性细胞毒性T淋巴细胞对抗半抗原抗体反应的抑制作用:I-A相关抗原在靶B淋巴细胞上的作用
J Immunol. 1982 Jul;129(1):63-9.
4
Analysis of Ir gene control of cytotoxic response to hapten-modified self: helper T cells specific for a sulfhydryl hapten can substitute for an anti-TNP-H-2b self helper cell defect.对半抗原修饰自身的细胞毒性反应的Ir基因控制分析:对巯基半抗原特异的辅助性T细胞可替代抗三硝基苯-H-2b自身辅助性T细胞缺陷。
J Immunol. 1981 Sep;127(3):940-5.
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Cell-mediated lympholytic responses against autologous cells modified with haptenic sulfhydryl reagents. I. Effector cells can recognize two distinct classes of hapten-reactive self sites on cell surface proteins.针对用半抗原巯基试剂修饰的自体细胞的细胞介导的淋巴细胞溶解反应。I. 效应细胞可识别细胞表面蛋白上两类不同的半抗原反应性自身位点。
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Human cytotoxic T cell responses to trinitrophenyl hapten and influenza virus. Diversity of restriction antigens and specificity of HLA-linked genetic regulation.人类细胞毒性T细胞对三硝基苯半抗原和流感病毒的反应。限制性抗原的多样性及HLA连锁基因调控的特异性。
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Interleukin-2 induction of hapten-specific cytolytic T cells in nude mice.白细胞介素-2在裸鼠中诱导半抗原特异性细胞毒性T细胞。
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Molecular requirements for trinitrophenyl recognition by antihapten cytotoxic T lymphocytes.抗半抗原细胞毒性T淋巴细胞识别三硝基苯基的分子要求。
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10
In vivo immunisation and reaction against TNP-modified splenocytes.体内针对三硝基苯修饰的脾细胞的免疫接种及反应。
Nature. 1978 Aug 24;274(5673):806-8. doi: 10.1038/274806a0.

引用本文的文献

1
Cytotoxic T lymphocytes discriminate between isomeric forms of the same hapten.细胞毒性T淋巴细胞能够区分同一半抗原的异构形式。
Immunology. 1986 Apr;57(4):499-504.

本文引用的文献

1
The somatic generation of immune recognition.免疫识别的体细胞产生
Eur J Immunol. 1971 Jan;1(1):1-9. doi: 10.1002/eji.1830010102.
2
Cell-mediated cell lysis in vitro: genetic control of killer cell production and target specificities in the mouse.体外细胞介导的细胞裂解:小鼠中杀伤细胞产生和靶细胞特异性的遗传控制。
Eur J Immunol. 1974 May;4(5):378-87. doi: 10.1002/eji.1830040514.
3
Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Confirmation of genetic control of response to trinitrophenyl-modified H-2 antigens by the use of anti-H-2 and anti-Ia antibodies.三硝基苯基修饰的自体淋巴细胞的细胞介导淋巴细胞溶解。通过使用抗H-2和抗Ia抗体证实对三硝基苯基修饰的H-2抗原反应的遗传控制。
J Exp Med. 1976 Jan 1;143(1):211-7. doi: 10.1084/jem.143.1.211.
4
Cross-reactive lysis of trinitrophenyl (TNP)-derivatized H-2 incompatible target cells by cytolytic T lymphocytes generated against syngeneic TNP spleen cells.针对同基因三硝基苯(TNP)脾细胞产生的细胞毒性T淋巴细胞对三硝基苯衍生化的H-2不相容靶细胞的交叉反应性裂解。
J Exp Med. 1976 Dec 1;144(6):1609-20. doi: 10.1084/jem.144.6.1609.
5
Evidence for direct linkage between antigen recognition and lytic expression in effector T cells.效应T细胞中抗原识别与裂解表达之间直接联系的证据。
J Exp Med. 1976 Mar 1;143(3):684-9. doi: 10.1084/jem.143.3.684.
6
Similar idiotypic specificity for the membrane IgD and IgM of human B lymphocytes.人类B淋巴细胞的膜IgD和IgM具有相似的独特型特异性。
J Immunol. 1975 Jan;114(1 Pt 1):250-2.
7
Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice.主要组织相容性复合体相关的免疫反应性是由低反应性小鼠的淋巴细胞在高反应性小鼠的胸腺中分化而获得的。
Proc Natl Acad Sci U S A. 1978 May;75(5):2439-42. doi: 10.1073/pnas.75.5.2439.
8
Regulation of T-cell-mediated lympholysis by the murine major histocompatibility complex. I. Preferential in vitro responses to trinitrophenyl-modified self K- and D-coded gene products in parental and F1 hybrid mouse strains.小鼠主要组织相容性复合体对T细胞介导的淋巴细胞溶解的调节。I. 亲代和F1杂交小鼠品系对三硝基苯基修饰的自身K和D编码基因产物的体外优先反应。
J Exp Med. 1979 Jun 1;149(6):1379-92. doi: 10.1084/jem.149.6.1379.
9
In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells.在辐射嵌合体中,嵌合宿主而非供体淋巴细胞的K或D区域决定了抗病毒细胞毒性T细胞的免疫反应性。
J Exp Med. 1978 Sep 1;148(3):805-10. doi: 10.1084/jem.148.3.805.
10
MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness.MHC 限制性细胞毒性 T 细胞:关于决定 T 细胞限制性特异性、功能及反应性的多态性主要移植抗原的生物学作用的研究。
Adv Immunol. 1979;27:51-177. doi: 10.1016/s0065-2776(08)60262-x.