Induction of primary antigen-specific immune reponses in SCID-hu-PBL by coupled T-B epitopes.
Adoptive transfer of human lymphoid cells into immunodeficient (SCID) mice lacking the ability to functionally rearrange T- and B-cell receptor genes constitutes a unique model to study and manipulate human immunocytes. We have investigated this model for the purpose of generating an antigen-specific primary humoral immune response. Peripheral blood lymphocytes (PBL) derived from blood donors were used to repopulate SCID mice, which subsequently were immunized with different B-cell epitopes coupled to either tetanus toxoid (TT), or to a promiscuous helper epitope of TT, or by incorporating the antigens into a liposome construct. By recruiting the necessary T-cell help found in the T-cell memory compartment against TT, primary immune responses were obtained against the hapten dinitrophenyl (DNP), the V3 loop peptide derived from glycoprotein (gp120) (HIV-1), the melanoma-associated GD2 ganglioside and ovine submaxillary mucin. The primary immune response against the GD2 ganglioside was induced by incapsulating TT into GD2-containing liposomes. These liposome constructs also allowed us to induce a high human IgG serotitre (3000-4000) against this normally not very immunogenic ganglioside.
Ifversen
P
P
Department of Immunotechnology, Lund University, Sweden.
Mårtensson
C
C
Danielsson
L
L
Ingvar
C
C
Carlsson
R
R
Borrebaeck
C A
CA
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004136:Dinitrobenzenes; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005732:Gangliosides; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D008081:Liposomes; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D009077:Mucins; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013745:Tetanus Toxoid
D004136:Dinitrobenzenes; D000939:Epitopes; D005732:Gangliosides; D007074:Immunoglobulin G; D008081:Liposomes; D009077:Mucins; D013745:Tetanus Toxoid; C019403:ganglioside, GD2