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.