HLA class II molecules influence susceptibility versus protection in inflammatory diseases by determining the cytokine profile.

HLA class II molecules influence susceptibility versus protection in inflammatory diseases by determining the cytokine profile.
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DOI:
10.4049/jimmunol.1201891
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发表时间:
2013-01-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
David CS
David CS
中科院分区:
其他
文献类型:
--
作者:
Mangalam AK;Taneja V;David CS

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人类的MHC编码最多态的基因,HLA基因,这对免疫系统清除感染至关重要。这可以归因于强大的选择压力,因为人口迁移到世界不同地区并遇到新的感染,导致新的HLA II类等位基因。HLA基因也具有最高的自身免疫性疾病的相对风险。三种单倍型-HLA-DR 2DQ 6、DR 4DQ 8和DR 3DQ 2-解释了HLA与大多数自身免疫性疾病的关联。我们假设这些单倍型,沿着它们的多种亚型,由于它们能够呈递致病肽以激活分泌细胞因子以清除感染的T细胞,因此在人类历史上的感染事件的瓶颈中幸存下来。不幸的是,它们也呈现自身肽/模拟物以激活自身反应性T细胞,从而分泌引起自身免疫性疾病的促炎细胞因子。
The MHC in humans encodes the most polymorphic genes, the HLA genes, which are critical for the immune system to clear infection. This can be attributed to strong selection pressure as populations moved to different parts of the world and encountered new kinds of infections, leading to new HLA class II alleles. HLA genes also have the highest relative risk for autoimmune diseases. Three haplotypes—HLA-DR2DQ6, DR4DQ8, and DR3DQ2—account for HLA association with most autoimmune diseases. We hypothesize that these haplotypes, along with their multiple subtypes, have survived bottlenecks of infectious episodes in human history because of their ability to present pathogenic peptides to activate T cells that secrete cytokines to clear infections. Unfortunately, they also present self-peptides/mimics to activate autoreactive T cells secreting proinflammatory cytokines that cause autoimmune diseases.
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