Acetylcholine receptor peptide recognition in HLA DR3-transgenic mice: In vivo responses correlate with MHC-peptide binding

R. Raju, E. G. Spack, C. S. David

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

HLA DR3 is an MHC molecule that reportedly predisposes humans to myasthenia gravis (MG). Though MG is an Ab-mediated autoimmune disease, CD4+ T cells are essential for the generation of high-affinity Abs; hence the specificities of autoreactive CD4+ T cells are important. In this study we report the HLA DR3-restricted T cell determinants on the extracellular region sequence of human acetylcholine receptor α subunit. We find two promiscuous determinants on this region 141-160 and 171-190 as defined by their immunogenicity in HLA DR3-, HLA DQ8-, and HLA DQ6-transgenic mice in the absence of endogenous mouse class II molecules. We also studied the minimal determinants of these two regions by truncation analysis, and the MHC binding affinity of a set of overlapping peptides spanning the complete sequence region of human acetylcholine receptor α subunit. One of the peptide sequences strongly immunogenic in HLA DR3-transgenic mice also had the highest binding affinity to HLA DR3. Identification of T cell determinants restricted to an MHC molecule known to predispose to MG may be an important step toward the development of peptide-based immunomodulation strategies for this autoimmune disease.

Original languageEnglish (US)
Pages (from-to)1118-1124
Number of pages7
JournalJournal of Immunology
Volume167
Issue number2
DOIs
StatePublished - Jul 15 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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