Disulfide trap MHC class I molecules and uses therefor
    2.
    发明授权
    Disulfide trap MHC class I molecules and uses therefor 有权
    二硫键捕获MHC I类分子及其用途

    公开(公告)号:US08992937B2

    公开(公告)日:2015-03-31

    申请号:US11846491

    申请日:2007-08-28

    摘要: A disulfide trap, comprising an antigen peptide covalently attached to an MHC class I heavy chain molecule by a disulfide bond extending between two cysteines, is disclosed. In some configurations, a disulfide trap, such as a disulfide trap single chain trimer (dtSCT), can comprise a single contiguous polypeptide chain. Upon synthesis in a cell, a disulfide trap oxidizes properly in the ER, and can be recognized by T cells. In some configurations, a peptide moiety of a disulfide trap is not displaced by high-affinity competitor peptides, even if the peptide binds the heavy chain relatively weakly. In various configurations, a disulfide trap can be used for vaccination, to elicit CD8 T cells, and in multivalent MHC/peptide reagents for the enumeration and tracking of T cells. Also disclosed are nucleic acids comprising a sequence encoding a disulfide trap. Such nucleic acids, which can be DNA vectors, can be used as vaccines.

    摘要翻译: 公开了包含通过在两个半胱氨酸之间延伸的二硫键共价连接到MHC I类重链分子上的抗原肽的二硫键。 在一些构型中,二硫键陷阱,例如二硫键捕获单链三聚体(dtSCT)可以包含单个连续的多肽链。 在细胞中合成时,二硫键在ER中正确氧化,可被T细胞识别。 在一些构型中,即使肽相对较弱地结合重链,二硫键陷阱的肽部分也不会被高亲和力的竞争者肽置换。 在各种构型中,二硫键可用于疫苗接种,引发CD8 T细胞和多价MHC /肽试剂,用于计数和追踪T细胞。 还公开了包含编码二硫键的序列的核酸。 可以使用这样的可以是DNA载体的核酸作为疫苗。