INDUCTION OF PRIMARY ANTIGEN-SPECIFIC IMMUNE-RESPONSES IN SCID-HU-PBLBY COUPLED T-B EPITOPES

Adoptive transfer of human lymphoid cells into immunodeficient (SCID) mice lacking the ability to functionally rearrange T- and B-cell recep tor genes constitutes a unique model to study and manipulate human imm unocytes. We have investigated this model for the purpose of generatin g an antigen-specific primary humoral immune response. Peripheral bloo d lymphocytes (PBL) derived from blood donors were used to repopulate SCID mice, which subsequently were immunized with different B-cell epi topes coupled to either tetanus toroid (TT), or to a promiscuous helpe r epitope of TT, or by incorporating the antigens into a liposome cons truct. By recruiting the necessary T-cell help found in the T-cell mem ory compartment against TT, primary immune responses were obtained aga inst the hapten dinitrophenyl (DNP), the V3 loop peptide derived from glycoprotein (gp120) (HIV-1), the melanoma-associated GD(2) gangliosid e and ovine submaxillary mucin. The primary immune response against th e GD(2) ganglioside was induced by incapsulating TT into GD(2)-contain ing liposomes. These liposome constructs also allowed us to induce a h igh human IgG serotitre (3000-4000) against this normally not very imm unogenic ganglioside.