Morrison L A, Lukacher A E, Braciale V L, Fan D P, Braciale T J
J Exp Med. 1986 Apr 1;163(4):903-21. doi: 10.1084/jem.163.4.903.
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.
我们通过控制呈递于靶细胞表面的病毒形式，研究了向一组MHC I类和II类限制性、流感病毒特异性CTL克隆提呈抗原的要求。H-2K/D和I区限制性CTL均可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裂解用灭活病毒制剂脉冲处理的组织相容性靶细胞。分离的流感血凝素（HA）多肽也可使靶细胞致敏，以供II类限制性、HA特异性CTL识别，但不能供I类限制性、HA特异性CTL识别。抑制新生病毒蛋白合成可消除靶细胞提呈与I类限制性CTL识别相关的病毒抗原的能力。值得注意的是，在暴露于灭活或感染性病毒制剂的靶细胞中，II类限制性识别的提呈不受影响。这种差异敏感性表明，这些H-2I区限制性CTL识别的是源自外源性引入病毒粒子的病毒多肽，而非感染细胞中新合成的病毒多肽。为支持这一论点，用溶酶体促渗剂氯喹处理靶细胞，可消除II类限制性CTL对感染靶细胞的识别，而不降低I类限制性CTL对感染靶细胞的识别。此外，当将流感HA基因导入无外源性HA多肽的靶细胞时，表达HA基因新合成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区限制性CTL在抗原提呈要求上可能存在重要差异。这些差异可能反映了这两个CTL亚群所识别的抗原表位的性质。
