Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones.

Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones.
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DOI:
10.1084/jem.163.4.903
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发表时间:
1986-04-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Braciale TJ
Braciale TJ
中科院分区:
其他
文献类型:
--
作者:
Morrison LA;Lukacher AE;Braciale VL;Fan DP;Braciale TJ

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我们通过控制呈递到靶细胞表面的病毒形式,检查了抗原呈递到一组MHC i类和ii类受限流感病毒特异性CTL克隆的要求。H-2K/D-和I区限制性CTL都能识别暴露于感染性病毒的靶细胞,但只有I区限制性克隆能有效地裂解用灭活病毒制剂脉冲的组织相容靶细胞。分离的流感血凝素(HA)多肽也能使靶细胞敏化,使其能够被ⅱ类限制性HA特异性CTL识别,而不能被ⅰ类限制性HA特异性CTL识别。抑制新生病毒蛋白合成使靶细胞无法呈递与i类限制性CTL识别相关的病毒抗原。值得注意的是,暴露于灭活病毒或感染性病毒制剂的靶细胞不受II类限制性识别的影响。这种不同的敏感性表明,这些限制H-2I区域的CTL识别来自外源引入的病毒粒子的病毒多肽,而不是在感染细胞中新合成的病毒多肽。为了支持这一论点,用促溶体剂氯喹治疗靶细胞,可以消除ii类限制性CTL对受感染靶细胞的识别,但不会减少i类限制性CTL对受感染靶细胞的识别。此外,当将流感HA基因导入没有外源性HA多肽的靶细胞时,表达新合成的HA基因蛋白产物的靶细胞仅被H-2K/ d限制性CTL识别。这些观察结果表明,H-2K/D和H-2I区域限制性CTL对抗原呈递的要求可能存在重要差异。这些差异可能反映了这两个CTL亚群识别的抗原表位的性质。
We have examined requirements for antigen presentation to a panel of MHC class I-and class II-restricted, influenza virus-specific CTL clones by controlling the form of virus presented on the target cell surface. Both H-2K/D- and I region-restricted CTL recognize target cells exposed to infectious virus, but only the I region-restricted clones efficiently lysed histocompatible target cells pulsed with inactivated virus preparations. The isolated influenza hemagglutinin (HA) polypeptide also could sensitize target cells for recognition by class II-restricted, HA-specific CTL, but not by class I-restricted, HA- specific CTL. Inhibition of nascent viral protein synthesis abrogated the ability of target cells to present viral antigen relevant for class I-restricted CTL recognition. Significantly, presentation for class II- restricted recognition was unaffected in target cells exposed to preparations of either inactivated or infectious virus. This differential sensitivity suggested that these H-2I region-restricted CTL recognized viral polypeptides derived from the exogenously introduced virions, rather than viral polypeptides newly synthesized in the infected cell. In support of this contention, treatment of the target cells with the lysosomotropic agent chloroquine abolished recognition of infected target cells by class II-restricted CTL without diminishing class I-restricted recognition of infected target cells. Furthermore, when the influenza HA gene was introduced into target cells without exogenous HA polypeptide, the target cells that expressed the newly synthesized protein product of the HA gene were recognized only by H-2K/D-restricted CTL. These observations suggest that important differences may exist in requirements for antigen presentation between H-2K/D and H-2I region-restricted CTL. These differences may reflect the nature of the antigenic epitopes recognized by these two CTL subsets.