AN ALTERED PEPTIDE LIGAND MEDIATES IMMUNE DEVIATION AND PREVENTS AUTOIMMUNE ENCEPHALOMYELITIS

被引:373
作者
NICHOLSON, LB
GREER, JM
SOBEL, RA
LEES, MB
KUCHROO, VK
机构
[1] BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,BOSTON,MA 02115
[3] EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA 02254
[4] HARVARD UNIV,SCH MED,WALTHAM,MA 02254
[5] STANFORD UNIV,VET ADM MED CTR,SCH MED,PALO ALTO,CA 94304
关键词
D O I
10.1016/1074-7613(95)90169-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, we have previously shown that the disease is mediated by Th1 cells, which recognize tryptophan 144 as the primary TCR contact point. Here we describe an altered peptide ligand (APL), generated by a single amino acid substitution (tryptophan to glutamine) at position 144 (Q144), which inhibits the development of EAE induced with the native PLP 139-151 peptide (W144). We show that the APL induces T cells that are cross-reactive with the native peptide and that these cells produce Th2 (IL-4 and IL-10) and Th0 (IFN gamma and IL-10) cytokines. Adoptive transfer of T cell lines generated with the APL confer protection from EAE. These data show that changing a single amino acid in an antigenic peptide can significantly influence T cell differentiation and suggest that immune deviation may be one of the mechanisms by which APLs can inhibit an autoimmune disease.
引用
收藏
页码:397 / 405
页数:9
相关论文
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