Neurons preferentially respond to self-MHC class I allele products regardless of peptide presented.
Neurons preferentially respond to self-MHC class I allele products regardless of peptide presented.
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DOI：
10.4049/jimmunol.0902159
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发表时间：
2010-01-15
期刊：
影响因子：
--
通讯作者：
Kaufman DL
中科院分区：
文献类型：
--
作者：
Escande-Beillard N;Washburn L;Zekzer D;Wu ZP;Eitan S;Ivkovic S;Lu Y;Dang H;Middleton B;Bilousova TV;Yoshimura Y;Evans CJ;Joyce S;Tian J;Kaufman DL
对缺乏MHC I类（MHC I）相关蛋白的小鼠的研究已经证明MHC I在神经发育中的作用。从这些观察中产生的一个中心问题是，神经元对MHC I的识别是否对MHC I等位基因产物和所呈现的肽具有特异性。利用成熟的胚胎视网膜外植体系统，我们观察到皮摩尔水平的重组自体mhc I分子抑制神经突的生长。然后，我们评估了一组重组可溶性MHC I的神经生物学活性，这些MHC I由不同的MHC I重链组成，具有定义的自我或非自我肽，用于培养具有不同MHC I单倍型的小鼠胚胎视网膜。我们观察到，无论呈现的肽的性质如何，自体MHC I等位基因产物比非自体MHC I分子具有更大的抑制神经活性，这种模式类似于某些先天免疫系统受体对MHC I的识别。然而，自身MHC I分子对MHC I缺陷小鼠的视网膜没有影响。这些观察结果表明，神经元对MHC I的识别可能与遗传MHC I等位基因协调，就像先天免疫系统中发生的那样。与这一观点一致，我们发现MHC I和MHC I受体在视网膜发育的早期阶段由前体细胞共同表达，这可能使这种协调成为可能。
Studies of mice lacking MHC class I (MHC I)-associated proteins have demonstrated a role for MHC I in neurodevelopment. A central question arising from these observations is whether neuronal recognition of MHC I has specificity for the MHC I allele product and the peptide presented. Using a well-established embryonic retina explant system, we observed that picomolar levels of a recombinant self-MHC I molecule inhibited neurite outgrowth. We then assessed the neurobiological activity of a panel of recombinant soluble MHC Is, consisting of different MHC I heavy chains with a defined self- or nonself-peptide presented, on cultured embryonic retinas from mice with different MHC I haplotypes. We observed that self-MHC I allele products had greater inhibitory neuroactivity than nonself-MHC I molecules, regardless of the nature of the peptide presented, a pattern akin to MHC I recognition by some innate immune system receptors. However, self-MHC I molecules had no effect on retinas from MHC I-deficient mice. These observations suggest that neuronal recognition of MHC I may be coordinated with the inherited MHC I alleles, as occurs in the innate immune system. Consistent with this notion, we show that MHC I and MHC I receptors are coexpressed by precursor cells at the earliest stages of retina development, which could enable such coordination.
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