Immunity：T细胞记忆机制 - 生物研究-生物谷

澳大利亚国立大学医学研究所，化学研究所的科学家发现新的免疫理论，相关成果公布在最新一期的 Immunity 上，并列为封面文章。
众所周知，B细胞具有记忆性，一般来说B细胞的记忆性的形成与DNA序列的改变有联系，B细胞通过改变DNA序列来维持细胞的记忆性。但是，免疫细胞的记忆性机制研究比较多的是B细胞，相比之下，T细胞研究的比较少。
研究小组发现，记忆性T细胞的分化过程中，RNA重排起重要作用。研究小组以小鼠的研究模型，通过沉默一个记忆性T细胞分化的关键基因ptprc（是产生记忆性T细胞CD45RO的重要基因），结果发现记忆性T细胞的比例发生改变。并且RNA结合蛋白hnRNALL发生改变，会导致RNA的识别区域变得不稳定。
研究者发现hnrpll突变会导致T细胞不在外周淋巴结聚集，但不影响增殖。对这些突变细胞进行外显子检测分析，结果发现记忆性T细胞的mRNA接过程发生的广泛的改变。并且相同的变化还出现在神经组织中，这可能是引发记忆性T细胞发生变化的原因。（生物谷Bioon.com）
生物谷推荐原始出处：
Immunity ,19 December 2008 doi:10.1016/j.immuni.2008.11.004
Memory T Cell RNA Rearrangement Programmed by Heterogeneous Nuclear Ribonucleoprotein hnRNPLL
Zuopeng Wu1,Xinying Jia2,Laura de la Cruz2,Xun-ChengSu2,Bruz Marzolf3,Pamela Troisch3,Daniel Zak3,Adam Hamilton1,BelindaWhittle1,Di Yu1,Daniel Sheahan1,Edward Bertram1,Alan Aderem3,GottfriedOtting2,Christopher C. Goodnow1,4,,andGerard F. Hoyne1,4
1 John Curtin School of Medical Research, Australian PhenomicsFacility, Australian National University, Canberra ACT 0200, Australia
2 Research School of Chemistry, Australian National University, Canberra ACT 0200, Australia
3 Institute for Systems Biology, 1441 North 34th St., Seattle, WA 98103-9804, USA
Corresponding author
4 These authors contributed equally
Summary
Differentiation of memory cells involves DNA-sequence changes in Blymphocytes but is less clearly defined in Tcells. RNA rearrangement isidentified here as a key event in memory Tcell differentiation byanalysis of a mouse mutation that altered the proportions of naive andmemory Tcells and crippled the process of Ptprc exon silencing needed togenerate CD45RO in memory Tcells. A single substitution inamemory-induced RNA-binding protein, hnRNPLL, destabilized anRNA-recognition domain that bound with micromolar affinity to RNAcontaining the Ptprc exon-silencing sequence. Hnrpll mutationselectively diminished Tcell accumulation in peripheral lymphoid tissuesbut not proliferation. Exon-array analysis of Hnrpll mutant naive andmemory Tcells revealed an extensive program of alternative mRNA splicingin memory Tcells, coordinated by hnRNPLL. A remarkable overlap withalternative splicing in neural tissues may reflect a co-opted strategyfor diversifying memory Tcells.