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HLA-DRA - 版本历史
2026-04-18T13:25:53Z
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2025年12月30日 (二) 11:29 77921020
2025-12-30T11:29:31Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2025年12月30日 (二) 11:29的版本</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <strong>HLA-DRA</strong>（Major Histocompatibility Complex, Class II, DR Alpha），即<strong>[[人类白细胞抗原]]-DR <del class="diffchange diffchange-inline">$\alpha$链</del></strong>。它是 [[MHC-II类分子]]（HLA-DR）的恒定亚基。与 [[HLA-A]]、[[HLA-B]] 或其伴侣 <strong>[[HLA-DRB1]]</strong> 展现出的惊人多态性（Polymorphism）截然不同，HLA-DRA 在人群中几乎是<strong>单态的</strong>（Monomorphic），即序列高度保守，极少发生变异。它与高度多态性的 <del class="diffchange diffchange-inline">$\beta$ </del>链（由 HLA-DRB1/3/4/5 编码）异源二聚化，形成功能性的 HLA-DR 受体，分布于<strong>[[抗原提呈细胞]] (APC)</strong> 表面。在临床医学中，HLA-DRA 编码蛋白在<strong>[[单核细胞]]</strong>表面的表达水平（即 <strong>mHLA-DR</strong>）是评估<strong>[[脓毒症]]</strong>患者免疫功能状态（免疫麻痹 vs 免疫风暴）的“金标准”生物标志物。此外，肿瘤细胞上的 MHC-II 类分子（包含 HLA-DRA）表达是预测<strong>[[PD-1抑制剂]]</strong>疗效的重要指标。</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <strong>HLA-DRA</strong>（Major Histocompatibility Complex, Class II, DR Alpha），即<strong>[[人类白细胞抗原]]-DR <ins class="diffchange diffchange-inline">α链</ins></strong>。它是 [[MHC-II类分子]]（HLA-DR）的恒定亚基。与 [[HLA-A]]、[[HLA-B]] 或其伴侣 <strong>[[HLA-DRB1]]</strong> 展现出的惊人多态性（Polymorphism）截然不同，HLA-DRA 在人群中几乎是<strong>单态的</strong>（Monomorphic），即序列高度保守，极少发生变异。它与高度多态性的 <ins class="diffchange diffchange-inline">β </ins>链（由 HLA-DRB1/3/4/5 编码）异源二聚化，形成功能性的 HLA-DR 受体，分布于<strong>[[抗原提呈细胞]] (APC)</strong> 表面。在临床医学中，HLA-DRA 编码蛋白在<strong>[[单核细胞]]</strong>表面的表达水平（即 <strong>mHLA-DR</strong>）是评估<strong>[[脓毒症]]</strong>患者免疫功能状态（免疫麻痹 vs 免疫风暴）的“金标准”生物标志物。此外，肿瘤细胞上的 MHC-II 类分子（包含 HLA-DRA）表达是预测<strong>[[PD-1抑制剂]]</strong>疗效的重要指标。</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l20" >第20行：</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> [[文件:HLA-DR_Structure.png|100px|HLA-DR 异源二聚体]]</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> [[文件:HLA-DR_Structure.png|100px|HLA-DR 异源二聚体]]</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">MHC-II 恒定 <del class="diffchange diffchange-inline">$\alpha$ </del>链</div></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">MHC-II 恒定 <ins class="diffchange diffchange-inline">α </ins>链</div></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l63" >第63行：</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 15px 0; text-align: justify;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 15px 0; text-align: justify;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> HLA-DRA 编码的 <del class="diffchange diffchange-inline">$\alpha$ </del>链与 <del class="diffchange diffchange-inline">$\beta$ </del>链共同构成 HLA-DR 分子，是连接先天免疫与适应性免疫的桥梁。</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> HLA-DRA 编码的 <ins class="diffchange diffchange-inline">α </ins>链与 <ins class="diffchange diffchange-inline">β </ins>链共同构成 HLA-DR 分子，是连接先天免疫与适应性免疫的桥梁。</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <ul style="padding-left: 25px; color: #334155;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <ul style="padding-left: 25px; color: #334155;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong>结构基础：</strong> HLA-DR 是一个异源二聚体，由 HLA-DRA (<del class="diffchange diffchange-inline">$\alpha$ </del>链) 和 HLA-DRB (<del class="diffchange diffchange-inline">$\beta$ </del>链) <del class="diffchange diffchange-inline">组成。$\alpha$ 链相对保守，提供结构稳定性；$\beta$ </del>链高度多变，负责特异性结合不同的肽段。两者共同形成<strong>[[肽结合槽]]</strong>，呈递外源性抗原给 <strong>[[CD4+ T细胞]]</strong>。</li></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong>结构基础：</strong> HLA-DR 是一个异源二聚体，由 HLA-DRA (<ins class="diffchange diffchange-inline">α </ins>链) 和 HLA-DRB (<ins class="diffchange diffchange-inline">β </ins>链) <ins class="diffchange diffchange-inline">组成。α 链相对保守，提供结构稳定性；β </ins>链高度多变，负责特异性结合不同的肽段。两者共同形成<strong>[[肽结合槽]]</strong>，呈递外源性抗原给 <strong>[[CD4+ T细胞]]</strong>。</li></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong>表达调控 (CIITA)：</strong> HLA-DRA 的转录严格受控于主调节因子 <strong>[[CIITA]]</strong> (MHC Class II Transactivator)。在炎症状态下，<strong>[[干扰素-γ]] (IFN-<del class="diffchange diffchange-inline">$\gamma$</del>)</strong> 是诱导 CIITA 及 HLA-DRA 表达的最强信号。</li></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong>表达调控 (CIITA)：</strong> HLA-DRA 的转录严格受控于主调节因子 <strong>[[CIITA]]</strong> (MHC Class II Transactivator)。在炎症状态下，<strong>[[干扰素-γ]] (IFN-<ins class="diffchange diffchange-inline">γ</ins>)</strong> 是诱导 CIITA 及 HLA-DRA 表达的最强信号。</li></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong>抗原加工途径：</strong></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong>抗原加工途径：</strong></div></td></tr>
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<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l114" >第114行：</td>
<td colspan="2" class="diff-lineno">第114行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <ul style="padding-left: 25px; color: #334155;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <ul style="padding-left: 25px; color: #334155;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong>免疫刺激疗法 (针对脓毒症)：</strong></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong>免疫刺激疗法 (针对脓毒症)：</strong></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <br><strong>[[干扰素-γ]] (IFN-<del class="diffchange diffchange-inline">$\gamma$</del>)</strong>、<strong>[[GM-CSF]]</strong>。</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <br><strong>[[干扰素-γ]] (IFN-<ins class="diffchange diffchange-inline">γ</ins>)</strong>、<strong>[[GM-CSF]]</strong>。</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <br><span style="font-size: 0.9em; color: #64748b;">*原理：这些细胞因子能强效诱导 [[CIITA]] 转录，恢复单核细胞表面的 HLA-DR 表达，逆转免疫麻痹，降低继发感染风险。临床试验正在进行中。</span></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <br><span style="font-size: 0.9em; color: #64748b;">*原理：这些细胞因子能强效诱导 [[CIITA]] 转录，恢复单核细胞表面的 HLA-DR 表达，逆转免疫麻痹，降低继发感染风险。临床试验正在进行中。</span></div></td></tr>
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2025-12-30T11:27:20Z
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<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>HLA-DRA</strong>（Major Histocompatibility Complex, Class II, DR Alpha），即<strong>[[人类白细胞抗原]]-DR $\alpha$链</strong>。它是 [[MHC-II类分子]]（HLA-DR）的恒定亚基。与 [[HLA-A]]、[[HLA-B]] 或其伴侣 <strong>[[HLA-DRB1]]</strong> 展现出的惊人多态性（Polymorphism）截然不同，HLA-DRA 在人群中几乎是<strong>单态的</strong>（Monomorphic），即序列高度保守，极少发生变异。它与高度多态性的 $\beta$ 链（由 HLA-DRB1/3/4/5 编码）异源二聚化，形成功能性的 HLA-DR 受体，分布于<strong>[[抗原提呈细胞]] (APC)</strong> 表面。在临床医学中，HLA-DRA 编码蛋白在<strong>[[单核细胞]]</strong>表面的表达水平（即 <strong>mHLA-DR</strong>）是评估<strong>[[脓毒症]]</strong>患者免疫功能状态（免疫麻痹 vs 免疫风暴）的“金标准”生物标志物。此外，肿瘤细胞上的 MHC-II 类分子（包含 HLA-DRA）表达是预测<strong>[[PD-1抑制剂]]</strong>疗效的重要指标。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">HLA-DRA · 基因档案</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Gene & Protein Profile (点击展开)</div><br />
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[[文件:HLA-DR_Structure.png|100px|HLA-DR 异源二聚体]]<br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">MHC-II 恒定 $\alpha$ 链</div><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc; width: 40%;">基因符号</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;"><strong>HLA-DRA</strong></td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">全称</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">MHC Class II DR Alpha</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">染色体位置</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">6p21.32 ([[MHC区域]])</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">Entrez ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">3122</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">HGNC ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">4947</td><br />
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<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">P01903</td><br />
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<th style="text-align: left; padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">分子量</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">~36 kDa (糖基化后)</td><br />
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<th style="text-align: left; padding: 8px 12px; color: #475569; background-color: #f8fafc;">关键搭档</th><br />
<td style="padding: 8px 12px; color: #0f172a;">[[HLA-DRB1]], [[CD4]]</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;">分子机制：抗原呈递的通用基座</h2><br />
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HLA-DRA 编码的 $\alpha$ 链与 $\beta$ 链共同构成 HLA-DR 分子，是连接先天免疫与适应性免疫的桥梁。<br />
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<li style="margin-bottom: 12px;"><strong>结构基础：</strong> HLA-DR 是一个异源二聚体，由 HLA-DRA ($\alpha$ 链) 和 HLA-DRB ($\beta$ 链) 组成。$\alpha$ 链相对保守，提供结构稳定性；$\beta$ 链高度多变，负责特异性结合不同的肽段。两者共同形成<strong>[[肽结合槽]]</strong>，呈递外源性抗原给 <strong>[[CD4+ T细胞]]</strong>。</li><br />
<li style="margin-bottom: 12px;"><strong>表达调控 (CIITA)：</strong> HLA-DRA 的转录严格受控于主调节因子 <strong>[[CIITA]]</strong> (MHC Class II Transactivator)。在炎症状态下，<strong>[[干扰素-γ]] (IFN-$\gamma$)</strong> 是诱导 CIITA 及 HLA-DRA 表达的最强信号。</li><br />
<li style="margin-bottom: 12px;"><strong>抗原加工途径：</strong><br />
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细胞通过吞噬或胞饮作用摄取外源蛋白，在[[溶酶体]]中将其降解为肽段。新合成的 HLA-DRA/B 在内质网中与 <strong>[[Ii链]] (CD74)</strong> 结合，运输至溶酶体样小室（MIIC），在此处 Ii 链被降解为 <strong>[[CLIP]]</strong>。在 <strong>[[HLA-DM]]</strong> 的辅助下，CLIP 被抗原肽置换，成熟的 MHC-II-肽复合物随后被转运至细胞膜。</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;">临床景观：免疫麻痹与肿瘤热度</h2><br />
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HLA-DRA 的表达水平（而非突变）是反映机体免疫状态的“晴雨表”。<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">疾病状态</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">生物标志物</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[脓毒症]] (Sepsis)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">mHLA-DR <strong>低表达</strong></td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">脓毒症后期常出现<strong>[[免疫麻痹]]</strong>（Immunoparalysis）。单核细胞表面的 HLA-DR (mHLA-DR) 表达量显著下降（通常 < 5000-15000 AB/cell）。这预示着患者清除病原体能力丧失，院内感染和死亡风险极高。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[肿瘤免疫治疗]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">MHC-II <strong>高表达</strong></td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">在黑色素瘤、乳腺癌等实体瘤中，肿瘤细胞或浸润淋巴细胞（[[TILs]]）高表达 HLA-DRA 提示肿瘤具有较强的免疫原性（“热肿瘤”），预测对 [[PD-1抗体]]（如[[帕博利珠单抗]]）疗效较好。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[自身免疫病]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">表达异常</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">在 [[系统性红斑狼疮]] (SLE) 和 [[类风湿性关节炎]] (RA) 中，HLA-DR 的异常高表达可能促进了自身抗原向 CD4+ T 细胞的呈递，加剧自身免疫反应。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[器官移植]]排斥</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">错配 (Mismatch)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">虽然 DRA 变异少，但供受者之间 HLA-DR 复合体的错配是诱发<strong>[[移植物抗宿主病]] (GVHD)</strong> 和急/慢性排斥反应的最主要原因之一。</td><br />
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针对 HLA-DRA（及 MHC-II）的干预主要是调节其表达水平，以逆转免疫抑制或增强抗肿瘤免疫。<br />
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<li style="margin-bottom: 12px;"><strong>免疫刺激疗法 (针对脓毒症)：</strong><br />
<br><strong>[[干扰素-γ]] (IFN-$\gamma$)</strong>、<strong>[[GM-CSF]]</strong>。<br />
<br><span style="font-size: 0.9em; color: #64748b;">*原理：这些细胞因子能强效诱导 [[CIITA]] 转录，恢复单核细胞表面的 HLA-DR 表达，逆转免疫麻痹，降低继发感染风险。临床试验正在进行中。</span><br />
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<li style="margin-bottom: 12px;"><strong>肿瘤疫苗与佐剂：</strong><br />
<br>设计包含 MHC-II 限制性表位（Epitope）的<strong>[[癌症疫苗]]</strong>，旨在激活 CD4+ 辅助 T 细胞，从而协助 CD8+ T 细胞产生更持久的抗肿瘤效应。</li><br />
<li style="margin-bottom: 12px;"><strong>表观遗传药物：</strong><br />
<br><strong>[[HDAC抑制剂]]</strong> 或 <strong>[[DNMT抑制剂]]</strong>。<br />
<br><span style="font-size: 0.9em; color: #64748b;">*机制：肿瘤细胞常通过启动子甲基化或组蛋白修饰沉默 MHC-II。使用表观遗传药物可去抑制，恢复 HLA-DRA 表达，使“冷肿瘤”变热。</span><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;">关键关联概念</h2><br />
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<li style="margin-bottom: 12px;"><strong>[[MHC-II类分子]]：</strong> HLA-DRA 所属的蛋白家族。</li><br />
<li style="margin-bottom: 12px;"><strong>[[单核细胞]]：</strong> 临床检测 HLA-DR 表达水平的主要细胞载体。</li><br />
<li style="margin-bottom: 12px;"><strong>[[免疫麻痹]] (Immunoparalysis)：</strong> 脓毒症中 HLA-DR 低表达所指示的病理状态。</li><br />
<li style="margin-bottom: 12px;"><strong>[[CIITA]]：</strong> HLA-DRA 转录的“总开关”。</li><br />
<li style="margin-bottom: 12px;"><strong>[[CD4+ T细胞]]：</strong> HLA-DR 呈递抗原的直接对象。</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</span><br />
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[1] <strong>Reith W, et al. (2005).</strong> <em>Regulation of MHC class II gene expression by the class II transactivator.</em> <strong>[[Nature Reviews Immunology]]</strong>. <br><br />
<span style="color: #475569;">[学术点评]：机制综述。详细解析了 CIITA 如何精细调控 HLA-DRA 等 MHC-II 基因的转录，是理解该领域表达调控的必读文献。</span><br />
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[2] <strong>Monneret G, et al. (2006).</strong> <em>Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock.</em> <strong>[[Intensive Care Medicine]]</strong>. <br><br />
<span style="color: #475569;">[学术点评]：临床金标准。确立了 mHLA-DR 低表达作为脓毒症免疫抑制和死亡风险预测因子的地位，推动了其在重症监护中的应用。</span><br />
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[3] <strong>Johnson DB, et al. (2016).</strong> <em>Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FGL1 signaling.</em> (注：更基础的关联见 <strong>Johnson DB, et al. (2016).</strong> <em>Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy.</em> <strong>[[Nature Communications]]</strong>). <br><br />
<span style="color: #475569;">[学术点评]：肿瘤免疫。证明了肿瘤细胞自主表达 MHC-II (HLA-DR) 是抗 PD-1 疗法产生应答的重要前提，揭示了 CD4+ T 细胞在抗肿瘤免疫中的直接作用。</span><br />
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[4] <strong>Chu, H.H., et al. (2011).</strong> <em>MHC class II transactivator (CIITA) is a specific target of the viral protein...</em> (注：关于病毒逃逸的机制)。 <br><br />
<span style="color: #475569;">[学术点评]：病毒逃逸。揭示了病毒如何通过抑制 CIITA 来下调 HLA-DRA，从而逃避 CD4+ T 细胞的监控，为感染免疫提供了机制解释。</span><br />
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[5] <strong>Meisel C, et al. (2009).</strong> <em>Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression...</em> <strong>[[American Journal of Respiratory and Critical Care Medicine]]</strong>. <br><br />
<span style="color: #475569;">[学术点评]：治疗干预。临床试验证明 GM-CSF 可以恢复脓毒症患者的 mHLA-DR 水平，为免疫刺激疗法提供了实证支持。</span><br />
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<div style="background-color: #0f172a; color: #ffffff; text-align: center; font-weight: bold; padding: 10px; letter-spacing: 1px;">HLA-DRA · 知识图谱关联</div><br />
<div style="padding: 15px; background: #ffffff; line-height: 2.2; text-align: center; text-decoration: none;"><br />
[[脓毒症]] • [[HLA-DRB1]] • [[MHC-II]] • [[CD4]] • [[免疫麻痹]] • [[干扰素-γ]] • [[PD-1抑制剂]] • [[CIITA]]<br />
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