Defining the structural requirements of a biologically active domain of human IL-1 beta.
The immunostimulatory activity in vivo of the pleiotropic cytokine IL-1 beta can be retained by its nonapeptide VQGEESNDK, in position 163-171. A series of shorter and longer peptides around this position has been assayed for IL-1-like biological activity, in order to identify the structural requirements for full expression of adjuvant capacity. Elongated peptides, comprising the loop region 165-169 and up to six amino acids in the preceding beta strand or up to seven amino acids in the following beta strand, showed activity comparable or lower than that of the nonapeptide 163-171. This would indicate that the beta strand sequences are not required for optimizing the active conformation of the immunostimulatory IL-1 beta moiety. Accordingly, stabilization of the 163-171 peptide conformation by cyclization did not increase its biological activity. In contrast, the pentapeptide GEESN, corresponding the exposed loop 165-169 between two beta strands, had biological activity higher than that of the 163-171 nonapeptide and fully comparable to that of the entire IL-1 beta protein. Thus, the highly exposed fragment 165-169 within the IL-1 beta molecule may be the structure selectively responsible for the IL-1 beta immunostimulatory capacity in vivo.
Boraschi
D
D
Laboratory of Immunopharmacology, Sclavo Research Center, Siena, Italy.
Antoni
G
G
Perin
F
F
Villa
L
L
Nencioni
L
L
Ghiara
P
P
Presentini
R
R
Tagliabue
A
A
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D010446:Peptide Fragments