LIPOSOME-ENTRAPPED T-CELL PEPTIDE PROVIDES HELP FOR A CO-ENTRAPPED B-CELL PEPTIDE TO OVERCOME GENETIC RESTRICTION IN MICE AND INDUCE IMMUNOLOGICAL MEMORY

We have investigated the possibility of a T-cell epitope peptide provi ding help for a B-cell epitope peptide when both peptides are co-entra pped in the same liposomes. Epitope models used were a 28 amino acid p eptide from the S region of the hepatitis B surface antigen (HBsAg) (s ubtype adw) containing an H-2(s) Th-cell epitope, and a 33 amino acid peptide from the pre-S-1 region of the HBsAg (subtype adw) designed to exclude an adjacent H-2(s) T-cell epitope, the latter (pre-S-1) pepti de being recognized by SJL (H-2(s)) mice as a B-cell epitope. SJL(H-2( s)) mice were immunized twice intramuscularly with S or pre-S-1 peptid e alone, co-entrapped in the same liposomes or entrapped in separate l iposomes which were mixed before injection. Analysis of sera for anti- peptide IgG1 antibodies revealed that the Th-cell peptide provided hel p for the pre-S-1 peptide only when the two peptides were co-entrapped in the same vesicles. This helper effect was found to correlate with the ability of S peptide (co-entrapped with the pre-S-1) to stimulate T-cell proliferation in vitro. There was no IgG1 response against pre- S-1 peptide in mice immunized with a mixture of the free peptides or a mixture of separately entrapped peptides. A helper effect, albeit muc h weaker, was also observed in mice immunized with the two peptides em ulsified in incomplete Freund's adjuvant. Antisera from mice immunized with both peptides co-entrapped in liposomes were found to bind to fu ll length (pre-S-1 containing) recombinant HBsAg. Moreover, binding va lues were much higher than those seen with antisera from animals immun ized with the liposomal S peptide above, presumably because of full ac cess of anti-pre-S-1 antibodies to the pre-S-1 region of the rHBsAg. I t is concluded that liposomes could serve not only as an immunological adjuvant for peptides but also as a carrier for Th- and B-cell epitop es thus eliminating the need for covalent linkage to a carrier protein .