HLA-DQ/human CD4-restricted immune response to cockroach allergens in transgenic mice

B. G. Papouchado, S. P. Chapoval, E. V. Marietta, C. R. Weiler, Chella S. David

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

We investigated the immune response to the German cockroach (Blattella germanica), and one of its major antigens, Blattella germanica group . 5 (Bla g 5), in a double-transgenic, double-knockout mouse expressing human HLA-DQ8, HLA-DQ6 and CD4 molecules in the absence of mouse class II and mouse CD4. Transgenic mice were primed and challenged with CR extract or individual synthetic peptides representing Bla g 5. Strong T-cell responses to CR extract were detected in both HLA-DQ/hCD4+ transgenic mice. The responses were two times lower in mice expressing HLA-DQ molecule in the context of mouse CD4. Under similar treatment, no responses were found in the double-knockout AB°/mCD4°mice and in mice expressing human CD4 molecule alone. HLA-DQ/hCD4 + mice produced primarily interleukin (IL)-5, IL-10, and IL-13. Minimal amounts of IL-4 were detected only in HL4-DQ6/hCD4+ mice. Interferon (IFN)-γ production was low in both transgenic mouse, suggesting a predominantly T-helper 2 (Th2)-type response. Cockroach allergen extract immunized HLA-DQ8/hCD4+ mice recognized only one of the 20 peptides of Bla g 5 while HLA-DQ6/hCD4+ mice responded primarily to three peptides. Primed with individual peptides, both HLA-DQ/hCD4+ mice responded maximally to peptides 10 (residues 91-110) and 17 (residues 161-180). In addition, HLA-DQ6/CD4+ mice responded to peptide 16 (residues 151-170). Thus, peptides 10 and 17 contained the major HLA-DQ-restricted hCD4+ T-cell epitopes and could be recognized by both HIh-DQ8 and HLA-DQ6 transgenic mice. Transgenic mice represent a new tool for investigating the immune responses to cockroach allergen. Our results suggest that therapeutic strategies aimed at developing antagonist peptides might be a useful treatment (immunotherapy) for allergic asthma.

Original languageEnglish (US)
Pages (from-to)303-311
Number of pages9
JournalTissue Antigens
Volume55
Issue number4
DOIs
StatePublished - May 15 2000

Keywords

  • Allergy
  • Antigens/peptides/epitopes
  • CD4
  • Cockroach
  • Cytokines
  • HLA-DQ
  • MHC class II
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Genetics

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  • Cite this

    Papouchado, B. G., Chapoval, S. P., Marietta, E. V., Weiler, C. R., & David, C. S. (2000). HLA-DQ/human CD4-restricted immune response to cockroach allergens in transgenic mice. Tissue Antigens, 55(4), 303-311. https://doi.org/10.1034/j.1399-0039.2000.550403.x