The response of bovine beta-lactoglobulin-specific T-cell clones to single amino acid substitution of T-cell core epitope.
Cow's milk is one of the most common food allergens in the first year of life, with approximately 2.5% of infants experiencing an allergic reaction to it. Beta-lactoglobulin (BLG) is one of the major allergens in cow's milk. Previously, we reported that four of six T-cell clones (TCC) which were established from cow's milk allergy patients recognized BLGp97-117 as the core sequence and also recognized BLG in association with the human leucocyte antigen (HLA)-DRB1*0405 allele. Using two of these four TCCs, we evaluated the T-cell response to BLG peptides with single amino acid substitution or deletion and identified BLGp102-112 as the minimum essential region in BLGp97-117. In the alanine-scan assay, the proliferative responses of TCCs to pE108A disappeared, and the proliferative responses of TCCs to pC106A decreased. In the analog peptide proliferation assay, pY102S had retained some T-cell response to the two TCCs. Collecting these results, we propose a motif for the interaction between the HLA-DRB1*0405 allele and antigen peptide, and suggest that BLGp105-108 are important residues to retain the TCR/BLG-peptide/HLA complex. pY102A and pY102S are partial agonists for the T-cell receptor. These peptides might be considered as candidate peptides for the modification of the T-cell response to BLG in cow's milk allergy.
Kondo
Masashi
M
Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
Kaneko
Hideo
H
Fukao
Toshiyuki
T
Suzuki
Kiyotaka
K
Sakaguchi
Heima
H
Shinoda
Shinji
S
Kato
Zenichiro
Z
Matsui
Eiko
E
Teramoto
Takahide
T
Nakano
Taku
T
Kondo
Naomi
N
D019943:Amino Acid Substitution / Q000276:immunology*; D000818:Animals; D002675:Child, Preschool; D002999:Clone Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D007782:Lactoglobulins / Q000276:immunology*; D008892:Milk / Q000276:immunology; D016269:Milk Hypersensitivity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007782:Lactoglobulins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma