Sakai K, Zamvil S S, Mitchell D J, Hodgkinson S, Rothbard J B, Steinman L
Department of Neurology and Genetics, Stanford University, CA 94305.
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9470-4. doi: 10.1073/pnas.86.23.9470.
Two synthetic immunodominant and nonencephalitogenic peptides of myelin basic protein, N1-20 and AcN9-20, effectively compete with an encephalitogenic peptide, AcN1-11, in an in vitro T-cell response restricted by class II major histocompatibility complex products (I-Au). These mutant peptide constructs, which do not occur in nature, also compete with the self-antigen for the in vivo induction of T cells primed with the encephalitogen AcN1-11. By using these nonpathogenic competitor peptides, it is possible to prevent the development of a prototypic T-cell-mediated autoimmune disease, experimental allergic encephalomyelitis. These results suggest possibilities for the utilization of competitor peptides for therapy of T-cell-mediated autoimmune diseases linked to specific major histocompatibility complex genes.
髓鞘碱性蛋白的两种合成免疫显性且无致脑炎性的肽段,N1 - 20和AcN9 - 20,在由II类主要组织相容性复合体产物(I - Au)限制的体外T细胞应答中,能有效地与一种致脑炎性肽段AcN1 - 11竞争。这些自然界中不存在的突变肽构建体,在体内也能与自身抗原竞争,以诱导用致脑炎原AcN1 - 11引发的T细胞。通过使用这些无致病性的竞争肽,有可能预防一种典型的T细胞介导的自身免疫疾病——实验性变应性脑脊髓炎的发展。这些结果提示了利用竞争肽治疗与特定主要组织相容性复合体基因相关的T细胞介导的自身免疫疾病的可能性。