A POLYALANINE PEPTIDE WITH ONLY 5 NATIVE MYELIN BASIC-PROTEIN RESIDUES INDUCES AUTOIMMUNE ENCEPHALOMYELITIS

被引:91
作者
GAUTAM, AM
PEARSON, CI
SMILEK, DE
STEINMAN, L
MCDEVITT, HO
机构
[1] STANFORD UNIV,MED CTR,SCH MED,DEPT CHEM,STANFORD,CA 94305
[2] STANFORD UNIV,MED CTR,SCH MED,DEPT NEUROL,STANFORD,CA 94305
[3] STANFORD UNIV,MED CTR,SCH MED,DEPT PEDIAT,STANFORD,CA 94305
[4] STANFORD UNIV,MED CTR,SCH MED,DEPT GENET,STANFORD,CA 94305
关键词
D O I
10.1084/jem.176.2.605
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The minimum structural requirements for peptide interactions with major histocompatibility complex (MHC) class II molecules and with T cell receptors (TCRs) were examined. In this report we show that substituting alanines at all but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not alter its ability to bind A-alpha(u)A-beta(u) (MHC class II molecules), to stimulate specific T cells and, surprisingly, to induce experimental autoimmune encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice. Most other amino acid side chains in the Ac1-11 peptide are essentially irrelevant for T cell stimulation and for disease induction. Further analysis revealed that binding to A-alpha(u)A-beta(u) occurred with a peptide that consists mainly of alanines and only three of the original residues of Ac1-11. Moreover, when used as a coimmunogen with MBP Ac1-11, this peptide inhibited EAE. The finding that a specific in vivo response can be generated by a peptide containing only five native residues provides evidence that disease-inducing TCRs recognize only a very short sequence of the MHC-bound peptide.
引用
收藏
页码:605 / 609
页数:5
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