Immune response of HLA-DQ transgenic mice to house dust mite allergen p2: identification of HLA-DQ restricted minimal epitopes and critical residues.
HLA-DQ8 (HLA-DQA1*0301; HLA-DQB1*0302) and HLA-DQ6 (HLA-DQA1*0103; HLA-DQB1*0602) genes were introduced into mouse class II (H-2A(o)(beta)) knockout mice. Transgenic HLA-DQ8 and HLA-DQ6 mice were individually immunized and challenged using synthetic peptides representing HDM (Dermatophagoides pteronyssinus) allergen p2. HLA-DQ8 mice responded to p2 peptides 1-20, 41-60, 51-70, 61-80, 91-110, and 101-120. HLA-DQ6 mice responded to peptides 1-20, 11-30, 21-40, 41-60, and 51-70. Using single amino acid truncated 30-mer peptides, residues necessary for HLA-DQ8 recognition were identified spanning regions 3-12, 50-70, and 91-120. A synthetic peptide comprising residues 3-12 was synthesized and a series of single alanine substitutions was introduced into the minimal peptide. Introduction of alanine residues at positions 3, 11, and 12 resulted in a significant loss of immune recognition. It was concluded that residues 4, 5, 7, 11, and 12 are critical for immune recognition by HLA-DQ8 mice.
Krco
C J
CJ
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Harders
J
J
Chapoval
S
S
David
C S
CS
D000818:Animals; D000917:Antibody Formation; D039741:Antigens, Dermatophagoides; D004391:Dust; D006023:Glycoproteins / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D008925:Mites / Q000276:immunology
D039741:Antigens, Dermatophagoides; D004391:Dust; D006023:Glycoproteins; D006683:HLA-DQ Antigens; D016056:Immunodominant Epitopes