HLA-DQ/human CD4-restricted immune response to cockroach allergens in transgenic mice.
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 Abetadegrees/mCD4degrees 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 HLA-DQ6/ hCD4+ mice. Interferon (IFN)-gamma 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/hCD4+ 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 HLA-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.
Papouchado
B G
BG
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Chapoval
S P
SP
Marietta
E V
EV
Weiler
C R
CR
David
C S
CS
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D020048:Blattellidae; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D006683:HLA-DQ Antigens; C063831:HLA-DQ6 antigen; C109756:HLA-DQ8 antigen