The effect on immunogenicity of coupling the immunostimulatory nonapeptide sequence (residues 163-171) from human interleukin 1f3 (IL-1if) to a small immunogen was examined. A 21-amino acid sequence spanning positions 12-32 on the large protein of hepatitis B surface antigen was chosen as a model. Three peptides were synthesized corresponding to the IL-13-derived sequence ], the hepatitis B surface antigen-derived sequence [peptide S1-(12-32)] and a composite peptide that included both these sequences separated by a spacer of two glycine residues [peptide S1-(12-32)-IL-(163-171)]. In an in vitro thymocyte proliferation assay, both peptides S1-(12-32)-IL-(163-171) and showed comparable activity, whereas peptide S1-(12-32) was inactive. Groups of five to seven mice each from C3H/CH, BALB/c, SJL/J, and C57BL/6 strains were immunized with equimolar amounts of either peptide S1-(12-32), peptide S1-(12-32)-IL-(163-171), or a mixture of peptides S1-(12-32) and IL-(163-171), and sera were screened for anti-S1-(12-32) antibodies. In all strains, peptide S1-(12-32)-IL-(163-171) elicited an increased primary and secondary anti-S1-(12-32) antibody response compared to the other two groups. Further, peptide S1-(12-32)- also induced an increased number of responders to primary immunization, though the number of responders was quantitative in all groups following secondary immunization. At least part of the enhanced immunogenicity of the S1-(12-32) sequence in peptide S1-(12-32)-IL-(163-171) appears to be due to augmented T-helper cell activity. These results suggest that coupling of the immunostimulatory IL-113derived sequence in tandem with an immunogen may confer inbuilt adjuvanticity.The cytokine interleukin 1 (IL-1) has been credited with a wide array of biological properties, which include amplification of both cellular and humoral immune responses to infectious or foreign agents (reviewed in refs. 1 and 2). Although precise details at the molecular level remain obscure, it is now widely believed that IL-1 plays an important role in T-and B-cell activation (1, 2). The immunoregulatory effects of IL-1 on T cells include enhanced proliferation in response to mitogen or antigen (3)(4)(5) and enhanced production of autocrine growth factors (3, 6). IL-1 has also been shown to act directly on B cells. It augments primary antibody responses both in vivo and in vitro (7-10) and can prime human B cells for subsequent activation (11). A B-cell growth and differentiation activity for IL-1 has also been described (12). Recently Uhl et al. (13) have identified IL-1 receptors on human monocytes, suggesting that initiation of the immune response by IL-1 can also be at the level of accessory cells.Though it has been suggested that IL-1 could serve as an adjuvant in conjunction with weakly immunogenic vaccines (14), its potent inflammatory activity (1, 2) restricts this application. Antoni et al. (15) have synthesized several short peptide fragments from hydrophilic sequences on human and murine IL-1 to determine the minima...