CEA-I2BM-Service de Recherches en Hemato-Immunologie, Paris, France.
PLoS One. 2011;6(7):e21011. doi: 10.1371/journal.pone.0021011. Epub 2011 Jul 14.
HLA-G is a natural tolerogenic molecule involved in the best example of tolerance to foreign tissues there is: the maternal-fetal tolerance. The further involvement of HLA-G in the tolerance of allogeneic transplants has also been demonstrated and some of its mechanisms of action have been elucidated. For these reasons, therapeutic HLA-G molecules for tolerance induction in transplantation are actively investigated. In the present study, we studied the tolerogenic functions of three different HLA-G recombinant proteins: HLA-G heavy chain fused to β2-microglobulin (B2M), HLA-G heavy chain fused to B2M and to the Fc portion of an immunoglobulin, and HLA-G alpha-1 domain either fused to the Fc part of an immunoglobulin or as a synthetic peptide. Our results demonstrate the tolerogenic function of B2M-HLA-G fusion proteins, and especially of B2M-HLA-G5, which were capable of significantly delaying allogeneic skin graft rejection in a murine in vivo transplantation model. The results from our studies suggest that HLA-G recombinant proteins are relevant candidates for tolerance induction in human transplantation.
HLA-G 是一种天然的免疫耐受分子，参与了最典型的免疫耐受实例：母婴耐受。HLA-G 进一步参与同种异体移植的耐受也已得到证实，其一些作用机制也已阐明。基于这些原因，用于移植中诱导免疫耐受的治疗性 HLA-G 分子正在被积极研究。在本研究中，我们研究了三种不同的 HLA-G 重组蛋白的免疫耐受功能：与 β2-微球蛋白（B2M）融合的 HLA-G 重链、与 B2M 和免疫球蛋白 Fc 部分融合的 HLA-G 重链，以及与免疫球蛋白 Fc 部分融合的 HLA-G alpha-1 结构域或作为合成肽。我们的结果表明 B2M-HLA-G 融合蛋白具有免疫耐受功能，特别是 B2M-HLA-G5，它能够在小鼠体内移植模型中显著延迟同种异体皮肤移植物排斥。我们的研究结果表明，HLA-G 重组蛋白是人类移植中诱导免疫耐受的候选物。
