Prediction of murine MHC class I epitopes in a major house dust mite allergen and induction of T1-type CD8+ T cell responses

Int Immunol. 1997 Feb;9(2):273-80. doi: 10.1093/intimm/9.2.273.

Abstract

The group I (Der p 1) allergen of Dermatophagoides pteronyssinus (house dust mite, HDM) contains several T helper (Th) epitopes recognized by C57BL/6 mice, with the peptide (111-139) containing a dominant MHC class II-restricted epitope (113-127). Since CD8+ T cells are thought to play a role in the regulation of allergic disease, we examined the Der p 1 sequence for potential MHC class I-binding motifs and observed that residues 111-119 (FGISNYCQI) contain motifs for H-2Db and Kb. Furthermore, immunization of C57BL/6 mice with unadjuvanted Ty virus-like particles (VLP) carrying Der p 1 (111-139), a method known to induce murine cytotoxic T lymphocyte (CTL) responses, primed Der p 1 (111-119)-specific Db-restricted CTL which produce high levels of IFN-gamma and low levels of IL-5 and IL-6 in vitro (T1-type CTL). VLP carrying the minimal epitope (FGISNYCQI) also induced a CTL response following immunization without adjuvant by various routes. Der p 1 (111-139)-VLP adjuvanted with alum did not prime CTL in C57BL/6 mice but were found to prime Th1-type CD4+ T cells that recognize the overlapping peptide (113-127) and native protein. The ability to successfully predict allergen-specific CD8+ T cell epitopes and prime CD8+ and/or CD4+ T cell responses provides an opportunity to dissect the relative roles of these T cells in the regulation of allergic responses and may offer therapeutic potential for reprogramming Th2-type allergic responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Allergens / immunology*
  • Animals
  • Antigens, Dermatophagoides
  • CD5 Antigens / immunology
  • CD8 Antigens / immunology
  • Cytokines / biosynthesis
  • Cytotoxicity Tests, Immunologic
  • Female
  • Genes, MHC Class I / immunology
  • Glycoproteins / immunology*
  • Immunodominant Epitopes / classification
  • Immunodominant Epitopes / immunology*
  • Injections, Intramuscular
  • Injections, Intraperitoneal
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Mites / immunology*
  • Spleen / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / physiology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism

Substances

  • Allergens
  • Antigens, Dermatophagoides
  • CD5 Antigens
  • CD8 Antigens
  • Cytokines
  • Glycoproteins
  • Immunodominant Epitopes