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Trends in Gene:免疫基因的突变或为器官移植带来麻烦

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8月3日,刊登在国际著名杂志<em>Trends in Genetics</em>上的一篇研究报告指出,人类的HLA(组织相容性抗原)基因进化比科学家认为的要快得多。这种进化上的改变可以改变我们抵御疾病的能力,HLA基因可以允许我们自身免疫系统区分自身细胞和外来侵入者。 HLA蛋白位于人类细胞表面,每一个个体在其细胞表面都有特异性的HLA蛋白,这些蛋白质可以扮演身份证...
8月3日,刊登在国际著名杂志<em>Trends in Genetics</em>上的一篇研究报告指出,人类的HLA(组织相容性抗原)基因进化比科学家认为的要快得多。这种进化上的改变可以改变我们抵御疾病的能力,HLA基因可以允许我们自身免疫系统区分自身细胞和外来侵入者。

HLA蛋白位于人类细胞表面,每一个个体在其细胞表面都有特异性的HLA蛋白,这些蛋白质可以扮演身份证的作用。拥有相同HLA的其它细胞被认为是自身细胞,外来的病毒或者细菌被认为是外来入侵者,免疫系统会及时识别并将其清理掉,我们的机体对于移植入的组织视为外来者,因此拒绝其的加入,除非病人和捐献者的HLA基因相同,因此,全世界的科学家正在努力去寻找可能的HLA突变体,希望提高病人和捐献者配对成功率。

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HLA的突变非常快速,研究者在现在的人口中建立了超过100万的突变体。尽全力去识别所有的突变体几乎不可能,因为这些基因进化的速度非常之快。当然了快速进化从某种意义上来说也是一种方便,因为这意味着,在人口水平上,我们的免疫系统变得更加可以抵御致病菌的感染了。对于移植器官接受者来说,配对成功的最佳机会是在一级亲属中寻找,而不是在全世界范围内寻找合适的捐献者。

编译自:<a title="" href="http://www.sciencedaily.com/releases/2012/08/120803121137.htm" target="_blank">Unexpected Variation in Immune Genes Poses Difficulties for Transplantation</a>
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<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080523014022.jpg" alt="" width="113" height="149" border="0" />

<a title="" href="http://dx.doi.org/doi:10.1016/j.tig.2012.06.007" target="_blank">doi:10.1016/j.tig.2012.06.007</a>
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<br/><strong>New reservoirs of HLA alleles: pools of rare variants enhance immune defense</strong><br/>


William Klitz1, , Philip Hedrick2, Edward J. Louis3

Highly polymorphic exons of the major histocompatibility complex (MHC, or HLA in humans) encode critical amino acids that bind foreign peptides. Recognition of the peptide–MHC complexes by T cells initiates the adaptive immune response. The particular structure of these exons facilitates gene conversion(GC) events, leading to the generation of new alleles. Estimates for allele creation and loss indicate that more than 10 000 such alleles are circulating at low frequencies in human populations. Empirical sampling has affirmed this expectation. This suggests that the MHC loci have a system for moving valuable and often complex variants into adaptive service. Here, we argue that HLA loci carry many new mutant alleles prepared to assume epidemiologically meaningful roles when called on by selection provoked by exposure to new and evolving pathogens. Because new mutant alleles appear in a population at the lowest possible frequency (i.e., a single copy), they have typically been thought of as having little consequence. However, this large population of rare yet potentially valuable new alleles may contribute to pathogen defense.

<br/>来源:生物谷

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