公开(公告)号：EP0722738A3

公开(公告)日：1996-10-23

申请号：EP95250317.5

申请日：1992-01-21

申请人： THE IMMUNE RESPONSE CORPORATION

发明人： Howell, Mark D. ,  Brostoff, Stephen W. ,  Carlo, Dennis J.

IPC分类号： A61K39/00 ,  A61K39/395 ,  A61K47/48 ,  A61K48/00 ,  G01N33/569

CPC分类号： C07K16/2809 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/53 ,  C07K14/7051 ,  C07K16/4258

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens complexed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific β-chain variable regions of T cell receptors, designated Vβ3, Vβ4, Vβ14 and Vβ17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

公开(公告)号：EP0722738A2

公开(公告)日：1996-07-24

申请号：EP95250317.5

申请日：1992-01-21

申请人： THE IMMUNE RESPONSE CORPORATION

发明人： Howell, Mark D. ,  Brostoff, Stephen W. ,  Carlo, Dennis J.

IPC分类号： A61K39/00 ,  A61K39/395 ,  A61K47/48 ,  A61K48/00 ,  G01N33/569

CPC分类号： C07K16/2809 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/53 ,  C07K14/7051 ,  C07K16/4258

摘要： The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens complexed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific β-chain variable regions of T cell receptors, designated Vβ3, Vβ4, Vβ14 and Vβ17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

摘要翻译： 本发明提供了疫苗和疫苗接种脊椎动物，以便防止或控制特定的T细胞介导的病状，包括自身免疫疾病和T细胞的未调节的复制的手段。 该疫苗是由T细胞受体（TCR）或它们对应于TCR本的T细胞介导的病理学的表面上的片段。 疫苗片段可以是对应于T细胞介导所述病理的特征的TCR的序列的肽。 这样的肽可以结合复合的MHC抗原呈递细胞上的抗原的常规或超抗原。 因此，提供为寻求疫苗确定性采矿适当的氨基酸序列的装置。 的疫苗施用于脊椎动物的方式做了诱导定向抗T的TCR的细胞介导的病理学免疫应答。 下调这种免疫应答或删除该致病性T细胞，从而消融所述疾病的发病机理。 本发明另外提供具体的β - 链式T细胞受体的可变区，被指定为V的β3，V的β4，V的β14和V 17的β，这是与自体免疫疾病，：如类风湿性关节炎（RA）的发病机制相关联，并且 多发性硬化（MS）。 因此，提供工具，以检测，预防和治疗RA和MS。 管理的DNA或RNA编码多肽的方法中有用的，作为本发明到个体的组织细胞的疫苗因此提供。