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MHC-I/抗原肽 - 版本历史
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<strong>[[MHC-I/抗原肽]] 复合物 (pMHC-I Complex)</strong> 是细胞免疫识别的物理核心，也是机体监控内部生物安全状态的“告示板”。它由 <strong>[[MHC-I]]</strong> 类分子的重链、$\beta_2$-微球蛋白以及长度通常为 8-10 个氨基酸的 <strong>内源性抗原肽</strong> 组成。该复合物主要在内质网中组装，随后转运至细胞表面，供 <strong>[[细胞毒性 T 细胞 (CTL)]]</strong> 的 TCR 扫描识别。这种机制确保了无论是病毒感染还是癌变导致的蛋白质异常，都能被免疫系统实时监测并清除。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">MHC-I/抗原肽</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">pMHC-I · 分子构造</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心任务：提呈内源性免疫信息</div><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">组成部分</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">$\alpha$ 链, $\beta_2$m, 抗原肽</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">肽段长度</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">8 - 10 氨基酸</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">结合位置</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">$\alpha_1$ 与 $\alpha_2$ 结构域</td><br />
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<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">CD8+ T 细胞 (CTL)</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">提呈路径</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">内源性抗原处理路径</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">生理意义</th><br />
<td style="padding: 8px 12px; color: #1e40af;">诱导细胞凋亡, 监控病毒</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">加工与组装：内源性提呈路径</h2><br />
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抗原肽与 MHC-I 的结合是一个多步骤的生化校对过程：<br />
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<li style="margin-bottom: 12px;"><strong>蛋白质降解：</strong> 细胞内的蛋白质（自身蛋白或病毒蛋白）被 <strong>[[泛素-蛋白酶体系统]]</strong> 降解为短肽。</li><br />
<li style="margin-bottom: 12px;"><strong>跨膜转运：</strong> 短肽通过 <strong>[[TAP]]</strong> (抗原处理相关转运体) 从胞浆进入内质网腔。</li><br />
<li style="margin-bottom: 12px;"><strong>复合物装配：</strong> 在分子伴侣（如 Tapasin）的协助下，符合裂隙大小的抗原肽嵌入 MHC-I 分子的肽结合槽中。</li><br />
<li style="margin-bottom: 12px;"><strong>胞面呈递：</strong> 组装稳定的复合物通过高尔基体转运至细胞膜表面，等待 <strong>[[TCR]]</strong> 的免疫检查。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">MHC-I 与 MHC-II 复合物对比</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">特征</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">[[MHC-I/抗原肽]]</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">[[MHC-II/抗原肽]]</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">抗原来源</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">内源性 (如病毒、胞质蛋白)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">外源性 (吞噬的病原体)</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">对应 T 细胞</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[CD8+ T (CTL)]]</strong></td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;"><strong>[[CD4+ T (Th)]]</strong></td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">肽结合槽形态</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">两端封闭</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">两端开放</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床应用：肿瘤新抗原与逃逸</h2><br />
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<li style="margin-bottom: 12px;"><strong>肿瘤新抗原 (Neoantigen)：</strong> 癌细胞的基因突变会产生不同于正常蛋白的“新抗原肽”，它们与 MHC-I 结合后可激发强效的 CTL 杀伤反应。这是个体化癌症疫苗的基础。</li><br />
<li style="margin-bottom: 12px;"><strong>免疫逃逸：</strong> 许多肿瘤细胞通过下调 <strong>[[MHC-I]]</strong> 的表达或抑制 <strong>[[TAP]]</strong> 功能，使“告牌”变空，从而逃避 CTL 的特异性识别。</li><br />
<li style="margin-bottom: 12px;"><strong>病毒策略：</strong> 疱疹病毒等通过阻断 MHC-I/抗原肽复合物的转运，实现长期慢性潜伏。</li><br />
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<li style="margin-bottom: 8px;"><strong>[[交叉提呈]] (Cross-presentation)：</strong> 树突状细胞将外源抗原加载到 MHC-I 上的特殊机制，对启动 CTL 响应至关重要。</li><br />
<li style="margin-bottom: 8px;"><strong>[[HLA]] (人类白细胞抗原)：</strong> 人类 MHC 的特定遗传学术语，决定了复合物的个体差异。</li><br />
<li style="margin-bottom: 8px;"><strong>[[抗原识别]]：</strong> TCR 与该复合物特异性契合的过程。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评 [Academic Review]</span><br />
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[1] <strong>Neefjes J, et al. (2011).</strong> <em>Towards a systems understanding of MHC class I and MHC class II antigen presentation.</em> <strong>[[Nature Reviews Immunology]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：目前对 MHC 类分子提呈路径及其与细胞器互动最系统的综述。</span><br />
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[2] <strong>Rock KL, et al. (2016).</strong> <em>Present Yourself! By MHC Class I and MHC Class II Molecules.</em> <strong>[[Trends in Immunology]]</strong>.<br><br />
<span style="color: #475569;">[学术点评]：详述了抗原肽如何被加工并精准嵌入 MHC 的分子动力学。</span><br />
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MHC-I/抗原肽 · 知识图谱<br />
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<td style="padding: 10px 15px; color: #334155;">[[TAP 转运体]]•[[蛋白酶体]]•[[分子伴侣 (Tapasin)]]</td><br />
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<td style="width: 110px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">分子识别</td><br />
<td style="padding: 10px 15px; color: #334155;">[[TCR-pMHC 相互作用]]•[[CD8 共受体结合]]</td><br />
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<td style="width: 110px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">调控轴</td><br />
<td style="padding: 10px 15px; color: #334155;">[[IFN-γ 诱导]]•[[US11/ICP47 (病毒抑制)]]</td><br />
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