A SOLUBLE DIVALENT CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE INHIBITS ALLOREACTIVE T-CELLS AT NANOMOLAR CONCENTRATIONS
A SOLUBLE DIVALENT CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE INHIBITS ALLOREACTIVE T-CELLS AT NANOMOLAR CONCENTRATIONS
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DOI：
10.1073/pnas.90.14.6671
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发表时间：
1993-07-15
影响因子：
11.1
通讯作者：
SCHNECK, JP
中科院分区：
文献类型：
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作者：
DALPORTO, J;JOHANSEN, TE;SCHNECK, JP
基因工程或化学纯化的可溶单价主要组织相容性复合体(MHC)分子以前曾用于研究T细胞，但并未阻止细胞毒性T细胞反应。在这里，我们描述了一种基因工程的二价I类MHC分子，它可以抑制同种异体反应性细胞毒性T细胞对靶细胞的裂解。该蛋白H-2K(B)/Ig G是小鼠第I类多肽H-2K(B)的胞外区与免疫球蛋白重链多肽之间的融合蛋白。该嵌合蛋白具有MHC多肽和Ig G多肽的血清学和生化特性。纳米分子浓度的H-2K(B)/Ig G不仅抑制同种异体反应性H-2K(B)特异性T细胞克隆对表达H-2K(B)的靶细胞的裂解，也抑制同种异体反应性H-2K(B)特异性原代T细胞的裂解。直接结合试验显示H-2K(B)/IgG分子与H-2K(B)特异性同种异体反应T细胞克隆之间有高亲和力结合。未标记的H-2K(B)/Ig G取代了I-125标记的H-2K(B)/Ig G，IC50为1.2 nM。
Genetically engineered or chemically purified soluble monovalent major histocompatibility complex (MHC) molecules, which have previously been used to study T cells, have not blocked cytotoxic T-cell responses. Here we describe a genetically engineered divalent class I MHC molecule which inhibits lysis of target cells by alloreactive cytotoxic T cells. This protein, H-2K(b)/IgG, was generated as a fusion protein between the extracellular domains of a murine class I polypeptide, H-2K(b), and an immunoglobulin heavy chain polypeptide. The chimeric protein has serological and biochemical characteristics of both the MHC and IgG polypeptides. Nanomolar concentrations of H-2K(b)/IgG inhibited lysis of H-2K(b)-expressing target cells not only by alloreactive H-2K(b)-specific T-cell clones but also by alloreactive H-2K(b)-specific primary T-cell cultures. A direct binding assay showed high-affinity binding between the H-2K(b)/IgG molecule and an H-2K(b)-specific alloreactive T-cell clone. Unlabeled H-2K(b)/IgG displaced I-125-labeled H-2K(b)/IgG from T cells with an IC50 of 1.2 nM.