ARD：白塞病风险变异HLA-B51/ERAP1-Hap10改变人类CD8 T细胞免疫

2022-08-31 彼岸河边草 MedSci原创

该研究结果表明，ERAP1-Hap10变异通过产生HLA-B51限制性肽参与白塞病(BD)发病机制，导致随后的CD8 T细胞反应的免疫优势发生变化。

目的：内质网氨肽酶(ERAP1)单倍型Hap10编码具有低酶活性的内质网(ER)驻留肽修整氨肽酶ERAP1的同种异型变异。这种单倍型隐性地赋予了在HLA-B*51携带者白塞病(BD)患者的最高风险。这种上位关系的机制含义和生物学后果尚不清楚。这个研究旨在确定其生物学相关性和功能影响。

方法：研究人员对26名未经治疗的土耳其BD受试者和22名健康供体进行基因分型和免疫表型分析，从HLA-B*51⁺ LCL生成CRISPR-Cas9 ERAP1 敲除细胞（KO），分析HLA I类结合肽组的肽长度差异并评估基因组编辑的细胞在CD8 T细胞共培养系统中的免疫原性。

结果：ERAP1-Hap10 的等位基因频率与以前的研究相似。在HLA-B*51背景中，ERAP1-Hap10的携带者和非携带者经抗原激活的CD8 T细胞和幼稚CD8 T细胞群的比例存在变化。与野生型对照细胞相比，ERAP1 KO细胞显示出具有更长肽段的肽组，肽段长度超过9聚体，并且它们刺激同种异体反应性CD8 T细胞的能力存在显著差异。

结论：该研究证明了低活性ERAP1改变了对CD8 T细胞的免疫原性，由带有欠修剪肽的HLA I类肽组介导。受影响携带者中的幼稚/效应CD8 T细胞转变提供了ERAP1-Hap10/HLA-B*51在细胞水平上的生物学证据，并指向HLA-B51受限的过程。该研究结果表明，ERAP1-Hap10变异通过产生HLA-B51限制性肽参与BD发病机制，导致随后的CD8 T细胞的免疫反应发生变化。

出处：Cavers A, Kugler MC, Ozguler Y, Al-Obeidi AF, Hatemi G, Ueberheide BM, Ucar D, Manches O, Nowatzky J. Behçet's disease risk-variant HLA-B51/ERAP1-Hap10 alters human CD8 T cell immunity. Ann Rheum Dis. 2022 Aug 3:annrheumdis-2022-222277. doi: 10.1136/ard-2022-222277. Epub ahead of print. PMID: 35922122.

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2022-11-27 1249857fm32暂无昵称

#RAP1#

54 0
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2023-06-08 124988c7m106暂无昵称

#ERA#

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2023-06-12 ms3153534357578991

#HLA-B#

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2022-08-30 12498dabm77暂无昵称

#变异#

47 0
[GetPortalCommentsPageByObjectIdResponse(id=1793050, encodeId=ff1b1e93050be, content=<a href='/topic/show?id=f821151215d' target=_blank style='color:#2F92EE;'>#RAP1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15121, encryptionId=f821151215d, topicName=RAP1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca282500032, createdName=1249857fm32暂无昵称, createdTime=Sun Nov 27 03:58:37 CST 2022, time=2022-11-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1739154, encodeId=a0571e3915426, content=<a href='/topic/show?id=6e566913df' target=_blank style='color:#2F92EE;'>#ERA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6913, encryptionId=6e566913df, topicName=ERA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e36234488643, createdName=124988c7m106暂无昵称, createdTime=Thu Jun 08 13:58:37 CST 2023, time=2023-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2005924, encodeId=6111200592495, content=<a href='/topic/show?id=37b78944ac' target=_blank style='color:#2F92EE;'>#HLA-B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8944, encryptionId=37b78944ac, topicName=HLA-B)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=606c2500035, createdName=ms3153534357578991, createdTime=Mon Jun 12 22:58:37 CST 2023, time=2023-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1343066, encodeId=9eab13430664e, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407648, encodeId=f300140e64819, content=<a href='/topic/show?id=f150e779256' target=_blank style='color:#2F92EE;'>#细胞免疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77792, encryptionId=f150e779256, topicName=细胞免疫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b9362684728, createdName=tulenzi, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502085, encodeId=5811150208553, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605421, encodeId=74db160542141, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=)]
2022-08-30 tulenzi

#细胞免疫#

53 0
[GetPortalCommentsPageByObjectIdResponse(id=1793050, encodeId=ff1b1e93050be, content=<a href='/topic/show?id=f821151215d' target=_blank style='color:#2F92EE;'>#RAP1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15121, encryptionId=f821151215d, topicName=RAP1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca282500032, createdName=1249857fm32暂无昵称, createdTime=Sun Nov 27 03:58:37 CST 2022, time=2022-11-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1739154, encodeId=a0571e3915426, content=<a href='/topic/show?id=6e566913df' target=_blank style='color:#2F92EE;'>#ERA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6913, encryptionId=6e566913df, topicName=ERA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e36234488643, createdName=124988c7m106暂无昵称, createdTime=Thu Jun 08 13:58:37 CST 2023, time=2023-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2005924, encodeId=6111200592495, content=<a href='/topic/show?id=37b78944ac' target=_blank style='color:#2F92EE;'>#HLA-B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8944, encryptionId=37b78944ac, topicName=HLA-B)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=606c2500035, createdName=ms3153534357578991, createdTime=Mon Jun 12 22:58:37 CST 2023, time=2023-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1343066, encodeId=9eab13430664e, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407648, encodeId=f300140e64819, content=<a href='/topic/show?id=f150e779256' target=_blank style='color:#2F92EE;'>#细胞免疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77792, encryptionId=f150e779256, topicName=细胞免疫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b9362684728, createdName=tulenzi, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502085, encodeId=5811150208553, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605421, encodeId=74db160542141, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=)]
2022-08-30 marongnuan

#HLA#

0 0
[GetPortalCommentsPageByObjectIdResponse(id=1793050, encodeId=ff1b1e93050be, content=<a href='/topic/show?id=f821151215d' target=_blank style='color:#2F92EE;'>#RAP1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15121, encryptionId=f821151215d, topicName=RAP1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca282500032, createdName=1249857fm32暂无昵称, createdTime=Sun Nov 27 03:58:37 CST 2022, time=2022-11-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1739154, encodeId=a0571e3915426, content=<a href='/topic/show?id=6e566913df' target=_blank style='color:#2F92EE;'>#ERA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6913, encryptionId=6e566913df, topicName=ERA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e36234488643, createdName=124988c7m106暂无昵称, createdTime=Thu Jun 08 13:58:37 CST 2023, time=2023-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2005924, encodeId=6111200592495, content=<a href='/topic/show?id=37b78944ac' target=_blank style='color:#2F92EE;'>#HLA-B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8944, encryptionId=37b78944ac, topicName=HLA-B)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=606c2500035, createdName=ms3153534357578991, createdTime=Mon Jun 12 22:58:37 CST 2023, time=2023-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1343066, encodeId=9eab13430664e, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407648, encodeId=f300140e64819, content=<a href='/topic/show?id=f150e779256' target=_blank style='color:#2F92EE;'>#细胞免疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77792, encryptionId=f150e779256, topicName=细胞免疫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b9362684728, createdName=tulenzi, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502085, encodeId=5811150208553, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605421, encodeId=74db160542141, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Tue Aug 30 22:58:37 CST 2022, time=2022-08-30, status=1, ipAttribution=)]
2022-08-30 ms691033630344116

#CD8#

47 0

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