HLA-DQ6 and HLA-DQ8 transgenic mice respond to ragweed allergens and recognize a distinct set of epitopes on short and giant ragweed group 5 antigens

Svetlana P. Chapoval, Teresa Neeno, Christopher J. Krco, Eric V. Marietta, Jerry Harders, Chella S. David

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Abstract

We have investigated the genetic and molecular basis of immune responsiveness to short ragweed (SRW) (Ambrosia artemisiifolia) extract, and group 5 allergens from short and giant (Ambrosia trifida) ragweed using transgenic mice expressing DQ6 (HLA-DQA1*0103, HLA-DQB1*0601) and DQ8 (HLA- DQA1*0301, HLA-DQB1*0302) genes in class II knockout (Aβ°) mice. Panels of overlapping peptides spanning the Amb a 5 and Amb t 5 Ags were synthesized. Mice were immunized with whole SRW extract or individual peptides s.c. and lymph node cells (LNC) were challenged in vitro. Strong T cell responses to SRW extract were measured in both HLA-DQ transgenic mice, while control, HLA-DQ6-/DQ8-/H-2Aβ°, mice were unresponsive. IL-5 and IL- 10 were the primary cytokines produced by in vitro challenged LNC of SRW- primed transgenic mice. HLA-DQ6-restricted T cell responses were detected to all three peptides of Amb t 5 and two determinants (residues 1-20 and 11-30) on Amb a 5. In contrast, LNC of HLA-DQ8 mice did not recognize peptide 11-30 of Arab t 5 Ag, but recognized several Amb a 5 determinants. The immune response in transgenic mice was dependent upon CD4+ T cells and was HLA-DQ restricted. Primed with purified Amb t 5, both transgenics recognized peptide 21-40, and an additional DQ6-restricted epitope was found within residue 1- 20. SRW-immunized HLA-DQ6 mice respond to peptide 11-30 of Amb a 5, while HLA-DQ8 mice strongly recognize peptide 1-20. These results demonstrate the specificity of HLA class II polymorphism in allergen sensitivity and pave the way for developing antagonistic peptides for desensitization.

Original languageEnglish (US)
Pages (from-to)2032-2037
Number of pages6
JournalJournal of Immunology
Volume161
Issue number4
StatePublished - Aug 15 1998

Fingerprint

Ambrosia
Allergens
Transgenic Mice
Epitopes
Antigens
Peptides
HLA-DQ Antigens
Lymph Nodes
T-Lymphocytes
MHC Class II Genes
HLA-DQ6 antigen
HLA-DQ8 antigen
Interleukin-5
Knockout Mice
Interleukin-10
Molecular Biology
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Chapoval, S. P., Neeno, T., Krco, C. J., Marietta, E. V., Harders, J., & David, C. S. (1998). HLA-DQ6 and HLA-DQ8 transgenic mice respond to ragweed allergens and recognize a distinct set of epitopes on short and giant ragweed group 5 antigens. Journal of Immunology, 161(4), 2032-2037.

HLA-DQ6 and HLA-DQ8 transgenic mice respond to ragweed allergens and recognize a distinct set of epitopes on short and giant ragweed group 5 antigens. / Chapoval, Svetlana P.; Neeno, Teresa; Krco, Christopher J.; Marietta, Eric V.; Harders, Jerry; David, Chella S.

In: Journal of Immunology, Vol. 161, No. 4, 15.08.1998, p. 2032-2037.

Research output: Contribution to journalArticle

Chapoval, SP, Neeno, T, Krco, CJ, Marietta, EV, Harders, J & David, CS 1998, 'HLA-DQ6 and HLA-DQ8 transgenic mice respond to ragweed allergens and recognize a distinct set of epitopes on short and giant ragweed group 5 antigens', Journal of Immunology, vol. 161, no. 4, pp. 2032-2037.
Chapoval, Svetlana P. ; Neeno, Teresa ; Krco, Christopher J. ; Marietta, Eric V. ; Harders, Jerry ; David, Chella S. / HLA-DQ6 and HLA-DQ8 transgenic mice respond to ragweed allergens and recognize a distinct set of epitopes on short and giant ragweed group 5 antigens. In: Journal of Immunology. 1998 ; Vol. 161, No. 4. pp. 2032-2037.
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abstract = "We have investigated the genetic and molecular basis of immune responsiveness to short ragweed (SRW) (Ambrosia artemisiifolia) extract, and group 5 allergens from short and giant (Ambrosia trifida) ragweed using transgenic mice expressing DQ6 (HLA-DQA1*0103, HLA-DQB1*0601) and DQ8 (HLA- DQA1*0301, HLA-DQB1*0302) genes in class II knockout (Aβ°) mice. Panels of overlapping peptides spanning the Amb a 5 and Amb t 5 Ags were synthesized. Mice were immunized with whole SRW extract or individual peptides s.c. and lymph node cells (LNC) were challenged in vitro. Strong T cell responses to SRW extract were measured in both HLA-DQ transgenic mice, while control, HLA-DQ6-/DQ8-/H-2Aβ°, mice were unresponsive. IL-5 and IL- 10 were the primary cytokines produced by in vitro challenged LNC of SRW- primed transgenic mice. HLA-DQ6-restricted T cell responses were detected to all three peptides of Amb t 5 and two determinants (residues 1-20 and 11-30) on Amb a 5. In contrast, LNC of HLA-DQ8 mice did not recognize peptide 11-30 of Arab t 5 Ag, but recognized several Amb a 5 determinants. The immune response in transgenic mice was dependent upon CD4+ T cells and was HLA-DQ restricted. Primed with purified Amb t 5, both transgenics recognized peptide 21-40, and an additional DQ6-restricted epitope was found within residue 1- 20. SRW-immunized HLA-DQ6 mice respond to peptide 11-30 of Amb a 5, while HLA-DQ8 mice strongly recognize peptide 1-20. These results demonstrate the specificity of HLA class II polymorphism in allergen sensitivity and pave the way for developing antagonistic peptides for desensitization.",
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