TY - JOUR
T1 - Immune response of HLA-DQ transgenic mice to house dust mite allergen p2
T2 - Identification of HLA-DQ restricted minimal epitopes and critical residues
AU - Krco, Christopher J.
AU - Harders, Jerry
AU - Chapoval, Svetlana
AU - David, Chella S.
N1 - Funding Information:
We thank Julie Hanson and her staff for outstanding mouse husbandry. We thank Dr. Dan McCormick and his staff (Jane Liebenow and Denise Walker) for superb technical support in synthesizing and purifying the peptides used in these investigations. We thank Mary Brandt for her secretarial assistance. This work was supported by NIH Grants AI 14764 and CA24473.
PY - 2000
Y1 - 2000
N2 - 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(β/°)), 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. (C) 2000 Academic Press.
AB - 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(β/°)), 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. (C) 2000 Academic Press.
KW - Allergy
KW - Epitopes
KW - HLA-DQ
KW - House dust mite
KW - Peptides
KW - T lymphocyte
KW - Transgenic
UR - http://www.scopus.com/inward/record.url?scp=0033778259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033778259&partnerID=8YFLogxK
U2 - 10.1006/clim.2000.4931
DO - 10.1006/clim.2000.4931
M3 - Article
C2 - 11027456
AN - SCOPUS:0033778259
SN - 1521-6616
VL - 97
SP - 154
EP - 161
JO - Clinical Immunology
JF - Clinical Immunology
IS - 2
ER -