{"id":90402,"date":"2019-04-18T00:00:50","date_gmt":"2019-04-23T04:18:28","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/90402\/"},"modified":"2019-04-23T12:18:33","modified_gmt":"2019-04-23T04:18:33","slug":"d16cba813e","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/90402\/","title":{"rendered":"\u3010\u4eae\u70b9\u5173\u6ce8\u3011Cell Discovery\uff1a\u8f7b\u94fe\u8c03\u8282\u91cd\u94fe\u6784\u8c61\u6539\u53d8\u9488\u5bf9\u7532\u578b\u6d41\u611f\u75c5\u6bd2\u7684\u5355\u514b\u9686\u6297\u4f53\u7684\u4fdd\u62a4\u7279\u6027"},"content":{"rendered":"
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\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011
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2019\u5e744\u670816\u65e5\uff0c<\/span>\u9ad8\u798f<\/strong><\/span>\u9662\u58eb\u56e2\u961f\u5728<\/span> Discovery<\/strong><\/em><\/span>\u4e0a\u53d1\u8868\u4e86\u9898\u4e3a\u201c<\/span>Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruses<\/strong><\/em><\/span>\u201d\u7684\u6587\u7ae0\uff0c<\/span>\u63a2\u7d22\u4e86\u4f7f\u7528\u8f7b\u94fe\u4fee\u9970\u6765\u5f00\u53d1\u9488\u5bf9\u7532\u578b\u6d41\u611f\u75c5\u6bd2\u548c\u5176\u4ed6\u65b0\u5174\u75c5\u6bd2\u7684\u5e7f\u6cdb\u4fdd\u62a4\u6027\u5355\u514b\u9686\u6297\u4f53\u7684\u7b56\u7565\uff0c\u4e3a\u7406\u89e3\u6297\u539f\u8bc6\u522b\u4e2d\u8f7b\u94fe\u7684\u5206\u5b50\u57fa\u7840\u63d0\u4f9b\u4e86\u91cd\u8981\u7ebf\u7d22\u3002<\/strong><\/span><\/span><\/span><\/p>\n

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\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011
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\u6d41\u611f\u75c5\u6bd2\u662f\u4e00\u79cd\u4e25\u91cd\u7684\u75c5\u539f\u4f53\uff0c\u5a01\u80c1\u7740\u5168\u7403\u516c\u5171\u5065\u5eb7\u5e76\u611f\u67d3\u4eba\u7c7b\u548c\u52a8\u7269\u79cd\u7fa4\u3002<\/span>\u5728\u4e0a\u4e2a\u4e16\u7eaa\uff0c\u5df2\u7ecf\u8bb0\u5f55\u4e86\u56db\u6b21\u6d41\u611f\u5927\u6d41\u884c\u5bfc\u81f4\u8bb8\u591a\u4eba\u6b7b\u4ea1\uff1a<\/span>1918\u5e74\u548c2009\u5e74\u7684H1N1\u30011957\u5e74\u7684H2N2\u3001\u4ee5\u53ca1968\u5e74\u7684H3N2\u3002\u867d\u7136\u5df2\u5177\u6709\u9488\u5bf9\u7532\u578b\u6d41\u611f\u75c5\u6bd2\u548c\u4e59\u578b\u6d41\u611f\u75c5\u6bd2\u7684\u75ab\u82d7\uff0c\u4f46\u7531\u4e8e\u6d41\u611f\u75c5\u6bd2\u682a\u7684\u5305\u819c\u86cb\u767d\uff08\u8840\u51dd\u7d20\uff0cHA;\u795e\u7ecf\u6c28\u9178\u9176\uff0cNA\uff09\u7684\u5feb\u901f\u6297\u539f\u6027\u53d8\u5f02\uff0c\u5b63\u8282\u6027\u6d41\u611f\u75ab\u82d7\u63d0\u4f9b\u7684\u4fdd\u62a4\u662f\u6709\u9650\u7684\u3002<\/span>\u56e0\u6b64\uff0c\u8feb\u5207\u9700\u8981\u901a\u7528\u75ab\u82d7\u548c\u6cbb\u7597\u6027\u6297\u4f53\u6765\u62b5\u6297\u90a3\u4e9b\u5feb\u901f\u53d8\u5316\u7684\u6d41\u611f\u75c5\u6bd2\u3002<\/span>
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\u5177\u6709\u5e7f\u6cdb\u4e2d\u548c\u4eba\u5355\u514b\u9686\u6297\u4f53\u4e3a\u7532\u578b\u6d41\u611f\u75c5\u6bd2\u611f\u67d3\u8005\u7684\u6cbb\u7597\u5230\u6765\u4e86\u5e0c\u671b\u3002<\/span>\u5927\u591a\u6570\u9488\u5bf9\u7532\u578b\u6d41\u611f\u75c5\u6bd2\u7684\u5e7f\u6cdb\u4e2d\u548c\u6297\u4f53\u7ed3\u5408\u4fdd\u5b88\u7684\u830e\u533a\u6216\u8840\u51dd\u7d20\u7684\u53d7\u4f53\u7ed3\u5408\u8154\uff0c\u5e76\u4e14\u76f8\u4e92\u4f5c\u7528\u7531\u91cd\u94fe\u652f\u914d\u3002<\/span>\u7136\u800c\uff0c\u8f7b\u94fe\u5bf9\u6297\u539f\u7684\u4f5c\u7528\u5f88\u5c0f\u6216\u6ca1\u6709\u76f4\u63a5\u63a5\u89e6\u3002<\/span>\u8fdb\u4e00\u6b65\u7684\u7ed3\u6784\u7814\u7a76\u8868\u660e\uff0c\u8f7b\u94fe\u901a\u8fc7\u5f71\u54cd\u91cd\u94fe\u7684\u5c40\u90e8\u6784\u8c61\u6765\u8c03\u8282\u4e2d\u548c\u8c31\uff0c\u800c\u4e0d\u662f\u4e0e\u6297\u539f\u76f4\u63a5\u76f8\u4e92\u4f5c\u7528\u3002<\/span><\/p>\n

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\u9ad8\u798f\u7814\u7a76\u56e2\u961f\u7b49\u4eba\u57fa\u4e8e\u4e8c\u4ee3\u6d4b\u5e8f\u6280\u672f\uff0c\u901a\u8fc7\u5bf9H7N9\u611f\u67d3\u60a3\u8005\u7684\u4e0d\u540c\u91cd\u94fe\u548c\u8f7b\u94fe\u7684\u7b5b\u9009\uff0c<\/span>\u83b7\u5f97\u4e86H3-\u8fdb\u5316\u679d\u5177\u6709\u4e2d\u548c\u6d3b\u6027\u7684\u4eba\u5355\u514b\u9686\u6297\u4f53AF4H1K1\uff0c\u8be5\u4eba\u5355\u514b\u9686\u6297\u4f53\u53ef\u8bc6\u522b\u6240\u67092\u7ec4\u7532\u578b\u6d41\u611f\u75c5\u6bd2\u7684\u8840\u51dd\u7d20\u7cd6\u86cb\u767d\u3002<\/strong><\/span>\u7ed3\u6784\u7814\u7a76\u8868\u660e\uff0c\u8f7b\u94fe\u901a\u8fc7\u5f71\u54cd\u91cd\u94fe\u7684\u5c40\u90e8\u6784\u8c61\u6765\u8c03\u8282\u4e2d\u548c\u8c31\uff0c\u800c\u4e0d\u662f\u4e0e\u6297\u539f\u76f4\u63a5\u76f8\u4e92\u4f5c\u7528\u3002<\/span>\u8fd9\u4e9b\u53d1\u73b0\u4e3a\u7406\u89e3\u6297\u539f\u8bc6\u522b\u4e2d\u8f7b\u94fe\u7684\u5206\u5b50\u57fa\u7840\u63d0\u4f9b\u4e86\u91cd\u8981\u7ebf\u7d22\uff0c\u5e76\u63a2\u7d22\u4e86\u7279\u522b\u662f\u4f7f\u7528\u8f7b\u94fe\u4fee\u9970\u6765\u5f00\u53d1\u9488\u5bf9\u7532\u578b\u6d41\u611f\u75c5\u6bd2\u548c\u5176\u4ed6\u65b0\u5174\u75c5\u6bd2\u7684\u5e7f\u6cdb\u4fdd\u62a4\u6027\u5355\u514b\u9686\u6297\u4f53\u7684\u7b56\u7565\u3002<\/span><\/strong><\/p>\n


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1\u3001\u901a\u8fc7NGS\u6280\u672f\u7b5b\u9009\u6297\u4f53<\/span><\/strong><\/p>\n

<\/span><\/strong>\u5c06\u6765\u81eaH7N9\u611f\u67d3\u7684\u60a3\u8005\u7684\u5916\u5468\u8840\u5355\u6838\u7ec6\u80de\uff08PBMC\uff09\u7684B\u7ec6\u80de\u53d7\u4f53\uff08\u5305\u62ec\u03bb-\u8f7b\u94fe\uff0c\u03ba-\u8f7b\u94fe\u548c\u91cd\u94fe\uff09\u7684\u53ef\u53d8\u533a\u57fa\u56e0\u5e93\u6269\u589e\uff0c\u6d4b\u5e8f\u5e76\u7528NGS\u5206\u6790\u3002\u6839\u636e\u4e92\u8865\u51b3\u5b9a\u533a3\uff08CDR3\uff09\u5e8f\u5217\u7684\u4e30\u5ea6\u548c\u957f\u5ea6\uff0c\u9009\u62e93\u4e2a\u91cd\u94feV\u57fa\u56e0\u548c5\u4e2a\u8f7b\u94feV\u57fa\u56e0\uff08 \u88681\uff09\u548c15\u4e2a\u914d\u5bf9\u7684IgG\u6297\u4f53\u4ea7\u751f\u3002\u5728\u8fd9\u4e9b\u914d\u5bf9\u7684IgG\u4e2d\uff0c<\/span>\u53d1\u73b0\u53ea\u6709\u4e00\u4e2a\u5e26\u6709\u91cd\u94feH1\u548c\u8f7b\u94feK1\u7684\u914d\u5bf9IgG\u53ef\u4ee5\u5728\u4f53\u5916\u4e2d\u548cH3N2 IAV\u800c\u4e0d\u662fH7N9\uff0c\u8be5MAb\u88ab\u547d\u540d\u4e3aAF4H1K1\u3002<\/span><\/strong><\/span><\/p>\n

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\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

<\/span>Table 1 Isotype and CDR3 sequence analysis for the selected three heavy chains and five light chains from an H7N9-infected patient
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2\u3001AF4H1K1\u53ef\u4ee5\u4e2d\u548cH3\u8fdb\u5316\u6811IAV<\/span><\/strong><\/p>\n

\u8fdb\u4e00\u6b65\u7684\uff0c\u7814\u7a76\u4eba\u5458\u5728\u4f53\u5916\u9a8c\u8bc1\u4e86\u4e86AF4H1K1\u5bf9IAV\u5176\u4ed6\u4e9a\u578b\u7684\u4e2d\u548c\u6d3b\u6027\u3002<\/span>\u7ed3\u679c\u663e\u793a\uff0c<\/span>AF4H1K1\u53ef\u4ee5\u4e2d\u548cH3-\u8fdb\u5316\u6811\u4e2d\u591a\u682a\u7532\u578b\u6d41\u611f\u75c5\u6bd2<\/strong><\/span>\uff1a<\/span>\u5305\u62ecH3\uff0cH4\u548cH14\uff0c50\uff05\u6291\u5236\u5242\u6d53\u5ea6\uff08IC50\uff09\u53ef\u8fbe13.2\u03bcg\/ml\u81f3189.0\u03bcg\/ ml\u3002<\/span>AF4H1K1\u53ef\u8bc6\u522b\u5728\u7b2c2\u7ec4IAV\u611f\u67d3\u7684\u7ec6\u80de\u8868\u9762\u8868\u8fbe\u7684\u6240\u6709HA\u86cb\u767d\u4e9a\u578b\uff0c\u4f46\u4e0d\u8bc6\u522b\u5728\u7b2c1\u7ec4IAV\u611f\u67d3\u7684\u7ec6\u80de\u4e2d\u8868\u8fbe\u7684HA\u86cb\u767d\u3002<\/span>AF4H1K1\u4ee5\u9ad8\u4eb2\u548c\u529b\u7ed3\u5408\u5927\u591a\u6570\u7b2c2\u7ec4HA\uff1a<\/span>\u5bf9\u4e8eH3\uff0cH4\uff0cH14\uff0cH7\u548cH10HA\uff0cKD\u503c<\/span>\u5206\u522b\u4e3a4pM\u81f349nM\u3002<\/span>\u76f8\u6bd4\u4e4b\u4e0b\uff0cAF4H1K1\u5bf9H15HA\u7684\u4eb2\u548c\u529b\u4f4e\u5f97\u591a\uff0cKD\u503c\u7ea6\u4e3a1.8\u03bcM\u3002<\/span><\/span><\/p>\n

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\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

Table 2 Neutralization activity of AF4H1L1, AF4H1K1, and AF4H1\/FI6L against a panel of IAVs from different groups<\/span><\/strong><\/p>\n


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  3\u3001AF4H1K1\/H3\u548cAF4H1K1\/H4\u590d\u5408\u7269\u7684\u6676\u4f53\u7ed3\u6784
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\u4e3a\u4e86\u786e\u5b9aAF4H1K1\u8bc6\u522b\u7684\u8868\u4f4d\uff0c\u7814\u7a76\u4eba\u5458\u89e3\u6790\u4e86AF4H1K1 Fab\u4e0e1968 H3N2\u5927\u6d41\u884c\u5206\u79bb\u682a\uff08H3-AC\/68\uff09\u548cH4N6\u9e2d\u5206\u79bb\u682a\uff08H4-CZ\/56\uff09\u7684\u590d\u5408\u7269\u7684\u6676\u4f53\u7ed3\u6784\u548c3.8\u00c5\u5206\u8fa8\u7387\u7ed3\u679c\u663e\u793a\uff0c\u4e24\u79cd\u914d\u5408\u7269\u7684\u603b\u4f53\u7ed3\u6784\u975e\u5e38\u76f8\u4f3c\u3002<\/span>AF4H1K1 Fab\u7247\u6bb5\u4ee5\u76f8\u4f3c\u7684\u65b9\u5411\u7ed3\u5408\u830e\u548c\u6b8b\u7559\u916f\u9176\u7ed3\u6784\u57df\u7684H3HA\u548cH4HA\uff0c\u5176\u4e2dFab\u5206\u5b50\u4e0eHA\u830e\u5927\u81f4\u6b63\u4ea4\u3002<\/span>\u5728\u4e24\u79cd\u590d\u6742\u7ed3\u6784\u4e2d\uff0c\u91cd\u94fe\u4e3b\u5bfc\u4e0eHA\u5206\u5b50\u7684\u76f8\u4e92\u4f5c\u7528\u3002<\/span>AF4H1K1\u91cd\u94fe\u7684\u7ed3\u5408\u8db3\u8ff9\u6d89\u53caHA1\u548cHA2\u4e9a\u57fa\uff0c\u800c\u8f7b\u94fe\u53ea\u63a5\u89e6HA2\u4e9a\u57fa\u7684\u4e24\u4e2a\u6c28\u57fa\u9178Gln42\u548cAsp46\uff0c\u5b83\u4eec\u4e5f\u53c2\u4e0e\u91cd\u94fe\u76f8\u4e92\u4f5c\u7528\u3002<\/span>\u5728AF4H1K1\u91cd\u94fe\u4e2d\uff0c\u91cd\u94feCDR1\uff08HCDR1\uff09\uff0cHCDR2\uff0cHCDR3\u548c \u91cd\u94fe\u6846\u67b6\u533a3\uff08HFR3\uff09\u73af\u53c2\u4e0eH3\u548cH4 HA\u5206\u5b50\u7684\u76f8\u4e92\u4f5c\u7528\u3002<\/span>\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u53ea\u6709\u8f7b\u94feCDR1\uff08LCDR1\uff09\u7684Ser30\uff0c Ser31\u548cTyr33\u4ee5\u53caLCDR3\u7684Gly93\u6709\u52a9\u4e8eH3 HA\u8868\u4f4d\u8bc6\u522b\uff0c\u800cLCDR3\u73af\u4e0d\u53c2\u4e0e\u8bc6\u522bH4\u5206\u5b50\u3002<\/span><\/p>\n

\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

Fig. 1: AF4H1K1 binding to the fusion subdomain of the HA trimer.<\/strong><\/span><\/strong> <\/span>
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4\u3001AF4H1L1\u548cAF4H1K1\u5206\u5b50\u7684\u7ed3\u6784\u6bd4\u8f83<\/span><\/strong><\/p>\n


<\/mpchecktext><\/span><\/strong><\/p>\n

AF4H1L1\u4e0d\u80fd\u7ed3\u5408\u6765\u81ea\u7ec42\u7684HA\uff0c\u4f8b\u5982H3\uff0cH4\uff0cH14\uff0cH7\uff0cH10\u548cH15\uff0c\u5982\u8868\u9762\u7b49\u79bb\u5b50\u4f53\u5171\u632f\uff08SPR\uff09\u6d4b\u5b9a\u6240\u793a\u3002\u4e0e\u7ed3\u5408\u8bd5\u9a8c\u4e00\u81f4\uff0cAF4H1L1\u4e0d\u80fd\u4e2d\u548c\u6765\u81ea\u7b2c1\u7ec4\u6216\u7b2c2\u7ec4\u7684IAV\uff08\u88682\uff09\u3002<\/span>\u4e3a\u4e86\u7406\u89e3\u4e3a\u4f55\u53ea\u6709\u8f7b\u94feK1\u53ef\u4ee5\u4e0e\u91cd\u94feH1\u5339\u914d\u4ee5\u83b7\u5f97HA\u7ed3\u5408\u548c\u4e2d\u548c\u6d3b\u6027\uff0c\u4f5c\u8005\u89e3\u6790\u4e86\u53e6\u4e00\u4e2aAF4H1L1\u7684Fab\u7ed3\u6784\u3002\u7ed3\u679c\u8868\u660e\uff0c<\/span>LCDR3\u5bf9HCDR3\u7684\u6784\u8c61\u53d8\u5316\u6709\u5f88\u5927\u7684\u8d21\u732e\uff0c\u800cHCDR3\u53c8\u51b3\u5b9a\u4e86MAb\u7684\u7ed3\u5408\u548c\u4e2d\u548c\u6d3b\u6027\u3002<\/strong><\/span>\u8be5\u7ed3\u679c\u8868\u660e\uff0c\u8f7b\u94fe\u901a\u8fc7\u8c03\u8282\u91cd\u94fe\u6784\u8c61\u5728MAb\u6d3b\u6027\u4e2d\u5177\u6709\u975e\u5e38\u91cd\u8981\u7684\u4f5c\u7528\uff0c\u5373\u4f7f\u8f7b\u94fe\u4e0e\u6297\u539f\u51e0\u4e4e\u6ca1\u6709\u76f4\u63a5\u76f8\u4e92\u4f5c\u7528\u3002<\/strong><\/span><\/p>\n

\u6b64\u5916\uff0c\u7814\u7a76\u8005\u5c06K1 CDR3\u6b8b\u57fa\u5f15\u5165L1\u4ee5\u4ea7\u751f\u4e00\u4e2a\u7a81\u53d8\u4f53AF4H1\/L1CDR3m\u3002\u8fc4\u4eca\u4e3a\u6b62\uff0c\u8be5\u7a81\u53d8\u4f53\u672a\u663e\u793a\u4efb\u4f55HA\u7ed3\u5408\u6216IAV\u4e2d\u548c\u6d3b\u6027\u3002\u6b64\u5916\uff0cAF4H1\/FI6v3L\uff0c\u4e00\u79cd\u6765\u81eaAF4H1K1\u7684\u91cd\u94fe\u548c\u6765\u81eaFI6v3\u7684\u8f7b\u94fe\u7684\u6742\u5408MAb\uff0c\u5728\u4f53\u5916\u6269\u5c55\u4e86H3-\u548cH7-\u8fdb\u5316\u679dIAV\u7684\u4e2d\u548c\u5bbd\u5ea6\u3002<\/strong> FI6v3\u8f7b\u94fe\u53ef\u901a\u8fc7\u5c06\u5176\u957fLCDR1\u73af\u63d2\u5165\u90bb\u8fd1\u7684HA\u5355\u4f53\u4e2d\u6765\u589e\u52a0AF4H1 \/ FI6v3L\u7684\u7ed3\u5408\u548c\u4e2d\u548c\u8c31\u3002<\/span>
<\/span><\/strong><\/span><\/p>\n

\u57fa\u4e8eAF4H1L1\uff0cAF4H1 \/ L1CDR3m\uff0cAF4H1K1\u548cAF4H1 \/ FI6v3L\u7684\u7ed3\u5408\u548c\u4e2d\u548c\u7ed3\u679c\u4ee5\u53ca\u7ed3\u6784\u5206\u6790\uff0c\u603b\u7ed3\u51fa\u6574\u4e2a\u8f7b\u94fe\u5728\u786e\u5b9a\u6297\u539f\u7ed3\u5408\u548c\u75c5\u6bd2\u4e2d\u548c\u4e2d\u5177\u6709\u5173\u952e\u4f5c\u7528\u3002<\/span><\/strong>\u7136\u800c\uff0c\u5355\u72ec\u7684LCDR3\u4e0d\u8db3\u4ee5\u589e\u5f3a\u6539\u53d8IgG\u884c\u4e3a\u7684\u5f3a\u5ea6\u3002
<\/span><\/strong><\/span><\/p>\n


<\/span><\/strong><\/span><\/p>\n

\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

Fig. 2: The interaction of AF4H1K1 VL and VH with H3 HA and H4 HA.<\/strong><\/span><\/strong>\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011
<\/p>\n

<\/strong>Fig. 3: Structural comparison between AF4H1K1 and AF4H1L1.<\/strong><\/span><\/strong><\/p>\n

\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

Fig. 4: Comparison of HA fusion subdomain-interacted domains of VH and VL from AF4H1K1 and FI6v3.<\/strong><\/span><\/strong><\/p>\n


<\/p>\n

4\u3001AF4H1K1\u7684\u9884\u9632\u548c\u6cbb\u7597\u529f\u6548<\/span><\/strong><\/span><\/span><\/p>\n

\u4e3a\u4e86\u8bc4\u4f30AF4H1K1 IgG \u52a8\u7269\u4f53\u5185\u5bf9H3\u4e9a\u578b\u6d41\u611f\u75c5\u6bd2\u7684\u4fdd\u62a4\u4f5c\u7528\uff0c\u7814\u7a76\u8005\u62ef\u6551\u4e86\u91cd\u7ec4\u75c5\u6bd2H3-rAC\/68\uff08HA\u6765\u81eaH3N2 A\/Aichi\/2\/1968\uff0c\u5269\u4f597\u4e2a\u57fa\u56e0\u7247\u6bb5\u6765\u81eaH1N1 A\/Puerto Rico\/8\/1934\uff09\u3002<\/span>\u8be5\u91cd\u7ec4\u75c5\u6bd2\u4e0d\u4f1a\u5728\u611f\u67d3\u7684\u5c0f\u9f20\u4e2d\u5f15\u8d77\u6b7b\u4ea1\uff0c\u4f46\u5728\u75c5\u6bd2\u611f\u67d3\u7684\u52a8\u7269\u7684\u80ba\u4e2d\u590d\u5236\u826f\u597d\u3002<\/span>\u56e0\u6b64\uff0c\u4f7f\u7528\u80ba\u4e2d\u7684\u75c5\u6bd2\u6ef4\u5ea6\u4f5c\u4e3a\u786e\u5b9aAF4H1K1\u7684\u4fdd\u62a4\u529f\u6548\u7684\u6307\u6807\uff0c\u5e76\u57fa\u4e8e\u80ba\u4e2d\u7684\u75c5\u6bd2\u590d\u5236\u786e\u5b9a50\uff05\u5c0f\u9f20\u611f\u67d3\u5242\u91cf\uff08MID50\uff09\u3002<\/span>\u9884\u9632\u4fdd\u62a4\u6548\u679c\u7814\u7a76\u4e2d\uff0c<\/span><\/strong><\/span>\u5728\u653b\u51fb\u524d1\u5929\u752815mg\/kg AF4H1K1\u5904\u7406\u7684\u5c0f\u9f20\u7684\u80ba\u4e2d\u7684\u75c5\u6bd2\u6ef4\u5ea6\u5206\u522b\u5728\u611f\u67d3\u540e3\u5929\u548c5\u5929\u51cf\u5c11\u7ea6500\u500d\u548c10,000\u500d\u3002<\/span>\u76f8\u53cd\uff0c\u9634\u6027\u5bf9\u7167\u6297\u57c3\u535a\u62c9 MAb 13C6 \u5bf9\u75c5\u6bd2\u6ef4\u5ea6\u6ca1\u6709\u4efb\u4f55\u660e\u663e\u7684\u5f71\u54cd\u3002<\/span>\u6cbb\u7597\u6027\u4fdd\u62a4\u6548\u679c\u7814\u7a76\u4e2d<\/span><\/strong><\/span>\uff0cAF4H1K1\u4e5f\u663e\u793a\u51fa\u6291\u5236 H3-rAC\/68 \u590d\u5236\u7684\u80fd\u529b\u3002<\/span>\u5728\u75c5\u6bd2\u653b\u51fb\u540e4,24\u548c48\u5c0f\u65f6\u540e\uff0c\u7528AF4H1K1\u621613C6IgG\u5904\u7406H3-rAC\/68\u611f\u67d3\u7684\u5c0f\u9f20\u3002<\/span>\u5728 3dpi \u65f6\uff0cAF4H1K1\u6cbb\u7597\u7ec4\u80ba\u90e848h\u7684\u75c5\u6bd2\u6ef4\u5ea6\u4f4e\u4e8e\u5bf9\u7167\u7ec4\uff0c\u800c 5dpi \u65f6\uff0c\u6240\u67093\u4e2aAF4H1K1\u6cbb\u7597\u7ec4\u5728\u4e0d\u540c\u65f6\u95f4\u70b9\u663e\u7740\u6291\u5236\u75c5\u6bd2\u590d\u5236\u3002<\/span>\u8fd9\u4e9b\u6570\u636e\u8868\u660eAF4H1K1\u5728\u4f53\u5185\u5177\u6709\u9488\u5bf9H3-rAC\/68\u611f\u67d3\u7684\u9884\u9632\u548c\u6cbb\u7597\u529f\u6548\u3002<\/span><\/span><\/p>\n

\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

Fig. 5: AF4H1K1 showed prophylactic and therapeutic activities against H3 and H7 IAVs.<\/strong><\/span><\/strong><\/strong><\/p>\n


<\/p>\n

<\/span><\/p>\n

ABSTRACT<\/span><\/strong><\/span><\/strong><\/span><\/strong><\/span><\/strong><\/span><\/p>\n

<\/span><\/span>The isolation of human monoclonal antibodies with broadly neutralizing breadth can provide a promising counter measure for influenza A viruses infection. Most broadly neutralizing antibodies against influenza A viruses bind to the conserved stem region or the receptor-binding cavity of hemagglutinin and the interaction is dominated by the heavy chain. The light chain, however, contributes few or no direct contacts to the antigen. Here we report an H3-clade neutralizing human monoclonal antibody, AF4H1K1, which recognizes the hemagglutinin glycoproteins of all group 2 influenza Aviruses. This human monoclonal antibody has been obtained through the screeningby pairing different heavy and light chains from an H7N9-infected patient based on the next-generation sequencing technology. Further structural studies revealed that light chains modulate the neutralizing spectrum by affecting the local conformation of heavy chains, instead of direct interaction with the antigen. These findings provide important clues to understand the molecular basis of light chains in antigen recognition and to explore the strategies in particular of the use of light chain modification to develop broadly protective monoclonal antibodies against influenza A viruses and other emerging viruses.<\/span><\/p>\n

<\/span>
<\/p>\n

\u539f\u6587\u94fe\u63a5\uff1a<\/span><\/strong><\/span><\/strong><\/span><\/p>\n

Haixia Xiao, Tianling Guo, Mi Yang, Jianxun Qi,Chaobin Huang, Yuanyuan Hong, Jinjin Gu, Xuefei Pang, William Jun Liu, RuchaoPeng, John McCauley, Yuhai Bi, Shihua Li, Junxia Feng, Hailiang Zhang, XupeiZhang, Xishan Lu, Jinghua Yan, Liling Chen, Yi Shi, Weizhi Chen & George FuGao.<\/span> Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruse<\/span><\/strong><\/em><\/span>. <\/span> Discovery<\/span><\/strong><\/span><\/em>, volume 5, Article number: 21 (2019).<\/span>
<\/p>\n

https:\/\/www.nature.com\/articles\/s41421-019-0086-x\/figures\/<\/span><\/strong><\/span><\/p>\n


<\/p>\n

\u672c\u671f\u7f16\u8f91\uff1a<\/span><\/strong><\/span>Annabella<\/span><\/p>\n

\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n

\"\u3010\u4eae\u70b9\u5173\u6ce8\u3011<\/p>\n<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"

2019\u5e744\u670816\u65e5\uff0c\u9ad8\u798f\u9662\u58eb\u56e2\u961f\u5728 Discovery\u4e0a\u53d1\u8868\u4e86\u9898\u4e3a\u201cLight chain modulate […]<\/p>\n","protected":false},"author":1,"featured_media":90403,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[2],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/90402"}],"collection":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/comments?post=90402"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/90402\/revisions"}],"predecessor-version":[{"id":90417,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/90402\/revisions\/90417"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/90403"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=90402"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=90402"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=90402"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}