Cao W, Tykodi S S, Esser M T, Braciale V L, Braciale T J
Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Nature. 1995 Nov 16;378(6554):295-8. doi: 10.1038/378295a0.
T cells are normally activated when the peptide for which they are specific is presented to them in the context of the appropriate major histocompatibility complex (MHC) (class I and Class II for CD8+ and CD4+ T cells, respectively). An increasing body of evidence indicates that structural homologues of the immunogenic peptide can partially activate or antagonize CD4+ T cells. CD8+ T cells may also be partially antagonized by such peptides, and self-derived peptides of this type may play a role in CD8+ T cell selection in the thymus. Activated CD8+ T cells lyse their targets by perforin-dependent granule exocytosis and by inducing apoptosis mediated by CD95 (also known as Fas or APO1) with its ligand (CD95L). Here we show that a clone of Kd-restricted CD8+ T cells specific for influenza haemagglutinin, which can also be activated in a crossreactive manner by a peptide derived from a myeloma tumour immunoglobulin heavy-chain variable region (IgVH) to kill by both routes, kills only by the CD95-CD95L pathway when stimulated by the corresponding germline IgVH peptide. As this germline IgVH peptide differs from the tumour peptide only at a single position buried in the MHC-binding groove, this indicates that CD95-CD95L-mediated killing can be triggered independently of the perforin-mediated pathway, and can be selectively affected by changes in MHC conformation.
当T细胞所特异性识别的肽在适当的主要组织相容性复合体（MHC）（分别针对CD8⁺和CD4⁺T细胞的I类和II类MHC）的背景下呈递给它们时，T细胞通常会被激活。越来越多的证据表明，免疫原性肽的结构同源物可以部分激活或拮抗CD4⁺T细胞。CD8⁺T细胞也可能被此类肽部分拮抗，并且这种类型的自身衍生肽可能在胸腺中CD8⁺T细胞的选择中发挥作用。活化的CD8⁺T细胞通过穿孔素依赖性颗粒胞吐作用以及通过诱导由CD95（也称为Fas或APO1）及其配体（CD95L）介导的凋亡来裂解其靶标。在这里，我们展示了一个针对流感血凝素的Kd限制性CD8⁺T细胞克隆，该克隆也可以被源自骨髓瘤肿瘤免疫球蛋白重链可变区（IgVH）的肽以交叉反应的方式激活，从而通过两种途径进行杀伤，但当受到相应的胚系IgVH肽刺激时，仅通过CD95 - CD95L途径进行杀伤。由于这种胚系IgVH肽与肿瘤肽仅在埋于MHC结合槽中的单个位置不同，这表明CD95 - CD95L介导的杀伤可以独立于穿孔素介导的途径被触发，并且可以受到MHC构象变化的选择性影响。
