Amino acid residue substitution at T-cell determinant-flanking sites in beta-lactoglobulin modulates antigen presentation to T cells through subtle conformational change.
We compared T-cell responses to regions in residues 21-40 of A and B variants of bovine milk beta-lactoglobulin (beta-LG) that vary by two different amino acid residues at 64 and 118. Results showed that T cells from C57/BL6 and C3H/HeN mice immunized with peptide 21-40 or BALB/c mice immunized with peptide 21-32 or 25-40 responded more vigorously to beta-LG B than to beta-LG A. This difference in response to 25-40 in BALB/c mice was not observed when beta-LGs B and A were denatured, suggesting that the conformation difference affects display of the determinant 25-40. Reactivity of anti-beta-LG monoclonal antibodies and molecular modeling using molecular dynamics calculations revealed subtle differences in the three-dimensional structure of these two variants. Furthermore, substitution of two amino acid residues at sites distant from the T-cell determinant induced differential determinant display on antigen-presenting cells, possibly due to subtle conformational changes in beta-LG.
Ametani
Akio
A
Department of Applied Biological Chemistry, The University of Tokyo, Japan.
Sakurai
Toshio
T
Katakura
Yoshinori
Y
Kuhara
Satoru
S
Hirakawa
Hideki
H
Hosoi
Tomohiro
T
Dosako
Shun-ichi
S
Kaminogawa
Shuichi
S
D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal; D017951:Antigen Presentation; D000941:Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002417:Cattle; D007156:Immunologic Memory; D007782:Lactoglobulins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D007782:Lactoglobulins