A SINGLE AMINO-ACID CHANGE IN A MYELIN BASIC-PROTEIN PEPTIDE CONFERS THE CAPACITY TO PREVENT RATHER THAN INDUCE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
A SINGLE AMINO-ACID CHANGE IN A MYELIN BASIC-PROTEIN PEPTIDE CONFERS THE CAPACITY TO PREVENT RATHER THAN INDUCE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
复制标题
DOI：
10.1073/pnas.88.21.9633
复制
发表时间：
1991-11-01
影响因子：
11.1
通讯作者：
MCDEVITT, HO
中科院分区：
文献类型：
--
作者：
SMILEK, DE;WRAITH, DC;MCDEVITT, HO
实验性自身免疫性脑脊髓炎（EAE）是啮齿类动物的一种实验性脱髓鞘疾病。在（PL/J x SJL）F1小鼠中，通过用髓鞘碱性蛋白肽Ac 1 -11免疫诱导。Ac 1 -11[4A]，一种具有单个氨基酸取代的髓鞘碱性蛋白肽类似物，（i）与II类主要组织相容性复合物分子结合，并在体外比Ac 1 -11更好地刺激致脑炎性T细胞，（ii）在体内是非免疫原性的和非致脑炎性的，（PL/J x SJL）F1小鼠，（iii）在用Ac 1 -11免疫之前或免疫时给药时预防EAE，和（iv）在接近疾病发作时较晚给药时预防EAE。初步研究表明，Ac 1 -11[4A]不能通过竞争性抑制或激活调节细胞来预防EAE。因此，髓鞘碱性蛋白肽中单个氨基酸的取代赋予预防而不是诱导EAE的能力，即使在肽特异性致脑炎T细胞已被激活之后。
Experimental autoimmune encephalomyelitis (EAE) is an experimental demyelinating disease of rodents. In (PL/J x SJL)F1 mice, it is induced by immunization with the myelin basic protein peptide Ac1-11. Ac1-11[4A], a myelin basic protein peptide analog with a single amino acid substitution, (i) binds to class II major histocompatibility complex molecules and stimulates encephalitogenic T cells in vitro better than Ac1-11, (ii) is nonimmunogenic and nonencephalitogenic in vivo in (PL/J x SJL)F1 mice, (iii) prevents EAE when administered before or at the time of immunization with Ac1-11, and (iv) prevents EAE when administered later, near the time of disease onset. Initial studies suggest that Ac1-11[4A] does not prevent EAE by competitive inhibition or by activation of regulatory cells. Thus, substitution of a single amino acid in a myelin basic protein peptide confers the capacity to prevent rather than induce EAE, even after peptide-specific encephalitogenic T cells have been activated.