Cryptic determinants and promiscuous sequences on human acetylcholine receptor: HLA-dependent dichotomy in T-cell function

Raghavanpillai Raju, Eric Marietta, Javier Vinasco, Bianca M. Conti-Fine, Anthony J. Infante, Chella S. David

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Experimental autoimmune myasthenia gravis can be induced in some strains of mice and rats by immunizing with acetylcholine receptor. Also, epidemiologic studies demonstrate an MHC linkage of myasthenia gravis in the man. In order to obtain direct experimental evidence for the influence of the genes of the MHC complex in the development of myasthenia gravis, we used mice transgenic to individual HLA molecules. We observed an increased susceptibility to the disease in HLA DQ8 transgenic mice compared to HLA DQ6 transgenic mice (J. Immunol. 160:4169; 1998). These mice lacked endogenous mouse class II molecules. In the present study we mapped the cryptic and dominant sequences on the extra cellular region of human acetylcholine receptor. Although some epitopes (e.g., α11-30, α141-160, α171-190) were common between DQ8 and DQ6 transgenic mice, several others were disparately recognized. We also found a functional dichotomy in T cells from mice differing by one MHC molecule (HLA DQ8 or DQ6) when primed by sequences immunodominant in DQ8 and DQ6 tg mice. Differential disease manifestation in the two different HLA transgenic mice could be explained not only by differential recognition of peptides by these antigen presenting molecules, but also by the difference in the functional profile of T cells generated when primed by promiscuous sequence regions.

Original languageEnglish (US)
Pages (from-to)237-247
Number of pages11
JournalHuman Immunology
Volume63
Issue number4
DOIs
StatePublished - Apr 23 2002

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Keywords

  • Antigen presentation
  • Autoimmunity
  • Cytokines
  • Myasthenia gravis
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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