ATM Influences the Efficiency of TCRβ Rearrangement, Subsequent TCRβ-Dependent T Cell Development, and Generation of the Pre-Selection TCRβ CDR3 Repertoire.docVIP

下载本文档

3
0
约4.41万字
约 9页
2017-05-07 发布于上海
举报
版权申诉

ATM Influences the Efficiency of TCRβ Rearrangement, Subsequent TCRβ-Dependent T Cell Development, and Generation of the Pre-Selection TCRβ CDR3 Repertoire.doc

1、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。。
2、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
3、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
6、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
7、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

ATM Influences the Efficiency of TCRβ Rearrangement, Subsequent TCRβ-Dependent T Cell Development, and Generation of the Pre-Selection TCRβ CDR3 Repertoire

ATMInfluencestheEfficiencyofTCRbRearrangement, SubsequentTCRb-DependentTCellDevelopment,and GenerationofthePre-SelectionTCRbCDR3Repertoire KarenS.Hathcock1*.,StevenBowen1.,FerencLivak2,RichardJ.Hodes1 1ExperimentalImmunologyBranch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,2DepartmentofMicrobiology andImmunology,UniversityofMarylandSchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica Abstract GenerationandresolutionofDNAdouble-strandbreaksisrequiredtoassembleantigen-specificreceptorsfromthegenes encoding V, D, and J gene segments during recombination. The present report investigates the requirement for ataxia telangiectasia-mutated(ATM)kinase,acomponentofDNAdouble-strandbreakrepair,duringTCRbrecombinationandin subsequent TCRb-dependent repertoire generation and thymocyte development. CD42CD82 double negative stage 2/3 thymocytes from ATM-deficient mice have both an increased frequency of cells with DNA break foci at TCRb loci and reduced Vb-DJb rearrangement. Sequencing of TCRb complementarity-determining region 3 demonstrates that ATM- + + deficientCD4 CD8 doublepositivethymocytesandperipheralTcellshavealteredprocessingofcodingendsforbothin- frame and out-of-frame TCRb rearrangements, providing the unique demonstration that ATM deficiency alters the expressedTCRbrepertoirebyaselection-independentmechanism.ATMKOthymiexhibitapartialdevelopmentalblockin + + DN cells as they negotiate the b-selection checkpoint to become double negative stage 4 and CD4 CD8 thymocytes, resulting in reduced numbers of CD4 CD8 cells. Importantly, expression of a rearranged TCRb transgene substantially + + + + reversesthisdefectinCD4 CD8 cells,directlylinkingarequirementforATMduringendogenousTCRbrearrangementto subsequentTCRb-dependentstagesofdevelopment.TheseresultsdemonstratethatATMplaysanimportantroleinTCRb rearrangement,generationoftheTCRbCDR3repertoire,andefficientTCRb-dependentTcelldevelopment. Citation: Hathcock KS, Bowen S, L