Biological activities on T lymphocytes of a baculovirus-expressed chimeric recombinant IgG1 antibody with specificity for the CDR3-like loop on the D1 domain of the CD4 molecule.
A baculovirus-expressed chimeric recombinant IgG1 (rIgG1) antibody, with Cgamma1 and Ckappa human constant domains, was derived from the murine monoclonal antibody (mAb) 13B8.2, which is specific for the CDR3-like loop of the CD4 molecule and which inhibits HIV-1 replication. Chimeric rIgG1 antibody 13B8.2 blocked, in a dose-dependent manner, antigen presentation through inhibition of subsequent IL-2 secretion by stimulated T cells. The one-way mixed lymphocyte reaction was abrogated by previous addition of baculovirus-produced rIgG1 13B8.2 in the T-cell culture. Anti-proliferative activity of rIgG1 was demonstrated on CD3-activated CD4+ T lymphocytes from healthy donors, such effect being associated with reduced IL-2 secretion of activated T cells. On the other hand, no proliferation inhibition was observed on CD4+ T lymphocytes activated with phorbol ester plus ionomycin, suggesting that rIgG1 13B8.2 preferentially acts on a proximal TCR-induced signaling pathway. Treatment of DBA1/J human CD4-transgenic mice with 100 microg of recombinant antibody for three consecutive days led to in vivo recovery of rIgG1 antibody 13B8.2 both coated on murine T lymphocytes and free in mouse serum, without CD4 depletion or down-modulation. These findings predict that the baculovirus-expressed chimeric rIgG1 anti-CD4 antibody 13B8.2 is a promising candidate for immunotherapy.
Troadec
Samuel
S
CNRS UMR 5160, Centre de Pharmacologie et Biotechnologie pour la Santé, Faculté de Pharmacie, 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, France.
Bès
Cédric
C
Chentouf
Myriam
M
Nguyen
Brigitte
B
Briant
Laurence
L
Jacquet
Chantal
C
Chebli
Karim
K
Pugnière
Martine
M
Roquet
Françoise
F
Cerutti
Martine
M
Chardès
Thierry
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000917:Antibody Formation / Q000276:immunology; D017951:Antigen Presentation / Q000187:drug effects; D000937:Antigen-Antibody Reactions / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D000939:Epitopes; D007074:Immunoglobulin G; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate