IDENTIFICATION OF CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX AND T-CELL RECEPTOR-BINDING SITES IN THE SUPERANTIGEN TOXIC SHOCK SYNDROME TOXIN-1
IDENTIFICATION OF CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX AND T-CELL RECEPTOR-BINDING SITES IN THE SUPERANTIGEN TOXIC SHOCK SYNDROME TOXIN-1
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DOI：
10.1084/jem.181.6.2229
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发表时间：
1995-06-01
影响因子：
15.3
通讯作者：
MATSUMURA, M
中科院分区：
文献类型：
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作者：
HURLEY, JM;SHIMONKEVITZ, R;MATSUMURA, M
与II类主要组织相容性复合体（MHC）分子结合的超抗原激活携带T细胞受体（TCR）的特定β链可变结构域的T细胞。与传统的肽抗原不同，超抗原作为完整的蛋白质与TCR和MHC分子在其肽结合位点之外结合。为了在分子水平上表征这些相互作用，在编码中毒性休克综合征毒素1（一种与中毒性休克综合征相关的细菌超抗原）的基因中产生随机点突变。功能受损的突变体的基础上，他们缺乏鼠和人的T细胞刺激活性，和实验分析结合人类组织相容性白细胞抗原-DR分子分化的残基参与MHC的TCR结合。结果表明，绝大多数突变聚集在中毒性休克综合征毒素1分子的两个不同区域。II类MHC结合位点位于NH 2-末端结构域的疏水区，TCR结合位点主要位于COOH-末端结构域的主要中央沟。这些研究提供了对人类超抗原介导的疾病所必需的相互作用的深入了解。
Superantigens, in association with class II major histocompatibility complex (MHC) molecules, activate T cells bearing particular beta chain variable domains of the T cell receptor (TCR). Unlike conventional peptide antigens, superantigens bind as intact proteins to TCR and MHC molecules outside their peptide binding sites. To characterize these interactions at the molecular level, random point mutations were generated in the gene encoding toxic shock syndrome toxin 1, a bacterial superantigen associated with toxic shock syndrome. Functionally impaired mutants were identified based on their lack of murine and human T cell stimulatory activities, and experiments analyzing binding to human histocompatibility leukocyte antigen-DR molecules differentiated residues involved in MHC from TCR binding. The results showed that the great majority of mutations are clustered in two distinct regions of the toxic shock syndrome toxin 1 molecule. The class II MHC binding site is located in the hydrophobic region bf the NH2-terminal domain, and the TCR binding site is primarily in the major central groove of the COOH-terminal domain. These studies provide insight into the interactions necessary for superantigen-mediated disease in humans.