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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Human inhibitory receptors lg-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class Ⅰ binding and bind preferentially to HLA-G
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Human inhibitory receptors lg-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class Ⅰ binding and bind preferentially to HLA-G

机译：人类抑制性受体Ig样转录物2（ILT2）和ILT4与CD8竞争MHCⅠ类结合，并优先结合HLA-G

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摘要

Ig-like transcript 4 (ILT4) (also known as leukocyte Ig-like receptor 2, CD85d, and LILRB2) is a cell surface receptor expressed mainly on myelomonocytic cells, whereas ILT2 (also known as leukocyte Ig-like receptor 1, CD85j, and LILRB1) is expressed on a wider range of immune cells including subsets of natural killer and T cells. Both ILTs contain immunoreceptor tyrosine-based inhibitory receptor motifs in their cytoplasmic tails that inhibit cellular responses by recruiting phosphatases such as SHP-1 (Src homology 2 domain containing tyrosine phosphatase 1). Although these ILTs have been shown to recognize a broad range of classical and nonclassical human MHC class I molecules (MHCIs), their precise binding properties remain controversial. We have used surface plasmon resonance to analyze the interaction of soluble forms of ILT4 and ILT2 with several MHCIs. Although the range of affinities measured was quite broad (K_d = 2-45μM), some interesting differences were observed. ILT2 generally bound with a 2- to 3-fold higher affinity than ILT4 to the same MHCI. Furthermore, ILT2 and ILT4 bound to HLA-G with a 3- to 4-fold higher affinity than to classical MHCIs, suggesting that ILT/HLA-G recognition may play a dominant role in the regulation of natural killer, T, and myelomonocytic cell activation. Finally, we show that ILT2 and ILT4 effectively compete with CD8 for MHCI binding, raising the possibility that ILT2 modulates CD8~+ T cell activation by blocking the CD8 binding as well as by recruiting inhibitory molecules through its immunoreceptor tyrosine-based inhibitory receptor motif.
机译：Ig样转录物4（ILT4）（也称为白细胞Ig样受体2，CD85d和LILRB2）是主要在粒单核细胞上表达的细胞表面受体，而ILT2（也称为白细胞Ig样受体1，CD85j，和LILRB1）在更广泛的免疫细胞中表达，包括自然杀伤细胞和T细胞的子集。两种ILT的胞质尾部均含有基于免疫受体酪氨酸的抑制性受体基序，这些基序通过募集磷酸酶（例如SHP-1）（含酪氨酸磷酸酶1的Src同源性2结构域）来抑制细胞反应。尽管已证明这些ILT能够识别广泛的经典和非经典人类I类MHC分子（MHCI），但它们的精确结合特性仍存在争议。我们已经使用表面等离子体激元共振来分析ILT4和ILT2的可溶形式与几种MHCI的相互作用。尽管测量的亲和力范围很广（K_d =2-45μM），但观察到一些有趣的差异。与相同的MHCI相比，ILT2的结合亲和力通常比ILT4高2至3倍。此外，ILT2和ILT4与HLA-G的亲和力比对传统MHCI的亲和力高3至4倍，这表明ILT / HLA-G的识别可能在自然杀伤，T和粒单核细胞的调节中起主要作用激活。最后，我们表明ILT2和ILT4与CD8有效竞争MHCI结合，从而提高了ILT2通过阻断CD8结合以及通过其基于免疫受体酪氨酸的抑制性受体募集抑制性分子来调节CD8 + T细胞活化的可能性。

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