Cullen C M, Jameson S C, DeLay M, Cottrell C, Becken E T, Choi E, Hirsch R
Division of Rheumatology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Cell Immunol. 1999 Feb 25;192(1):54-62. doi: 10.1006/cimm.1998.1434.
Activation of antigen-specific T cell clones in vivo might be possible by generating soluble MHC molecules; however, such molecules do not induce effective T cell responses unless cross-linked. As a first step in generating a soluble MHC molecule that could function as an antigen-specific immunostimulant, the extracellular domains of the murine H-2Kb MHC class I molecule were fused to the constant domains of a murine IgG1 heavy chain, resulting in a divalent molecule with both a TCR-reactive and an Fc receptor (FcR)-reactive moiety. The fusion protein can be loaded with peptide and can induce T cell activation in a peptide-specific, MHC-restricted manner following immobilization on plastic wells or following cross-linking by FcR+ spleen cells. The fusion protein induces partial T cell activation in vivo in a mouse transgenic for a TCR restricted to H-2Kb. This fusion protein molecule may be useful to study peptide-MHC interactions and may provide a strategy for boosting in vivo antigen-specific T cell responses, such as to viral or tumor antigens.
通过生成可溶性MHC分子，有可能在体内激活抗原特异性T细胞克隆；然而，此类分子除非交联，否则不会诱导有效的T细胞反应。作为生成可作为抗原特异性免疫刺激剂发挥作用的可溶性MHC分子的第一步，将小鼠H-2Kb MHC I类分子的胞外结构域与小鼠IgG1重链的恒定结构域融合，产生一种具有TCR反应性和Fc受体（FcR）反应性部分的二价分子。融合蛋白可负载肽，在固定于塑料孔上或经FcR+脾细胞交联后，能以肽特异性、MHC限制性方式诱导T细胞活化。该融合蛋白在体内可诱导TCR限于H-2Kb的小鼠转基因中部分T细胞活化。这种融合蛋白分子可能有助于研究肽-MHC相互作用，并可能提供一种增强体内抗原特异性T细胞反应（如针对病毒或肿瘤抗原的反应）的策略。
