Differential inhibition of IL-1 beta activities and receptor binding by monoclonal antibodies mapping within a discrete region of the protein.
The importance of the region in position 148-192 for the biological activities and receptor-binding capacity of the human IL-1 beta protein has been assessed by the use of mAbs. Four mAbs have been used, which recognize different epitopes within the 148-192 region. None of the mAbs could inhibit binding of IL-1 beta to IL-1RI (expressed on T cells and fibroblasts), suggesting that the 148-192 region does not contain IL-1RI binding sites. Conversely, mAbs Vhp20 (recognizing the fragment 166-169) and BRhD2 (directed to an epitope in the sequence 177-186) recognize sites partially involved in binding to IL-1RII (expressed on B cells, macrophages, and PMN). Only mAbs BRhD2 and FIB 1 (which recognizes an epitope in the sequence 174-186) can inhibit IL-1 beta-induced thymocyte proliferation, whereas all four can inhibit the adjuvant capacity of IL-1 beta in vivo. It is concluded that the region 148-192 encompasses domains important for T cell activation but not for binding to the IL-1RI on T cells, others involved in immunostimulation in vivo, and others important for binding to IL-1RII, although not directly involved in it.
Boraschi
D
D
Sclavo Research Center, Siena, Italy.
Villa
L
L
Ghiara
P
P
Presentini
R
R
Bossù
P
P
Censini
S
S
Nucci
D
D
Massone
A
A
Rossi
R
R
Flad
H D
HD
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002478:Cells, Cultured; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000276:immunology*; D017472:Receptors, Interleukin-1; D013950:Thymus Gland / Q000166:cytology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1