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
| Autor: | Françoise Roquet, Samuel Troadec, Thierry Chardès, Cédric Bès, Martine Cerutti, Martine Pugnière, Chantal Jacquet, Karim Chebli, Laurence Briant, Brigitte Nguyen, Myriam Chentouf |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
CD3 Complex medicine.drug_class T cell medicine.medical_treatment Recombinant Fusion Proteins T-Lymphocytes Immunology Antigen presentation Gene Expression Mice Transgenic Monoclonal antibody Major histocompatibility complex Lymphocyte Activation Cell Line Antigen-Antibody Reactions Epitopes Mice medicine Immunology and Allergy Animals Humans Cell Proliferation HIV Long Terminal Repeat Antigen Presentation biology Ionomycin T-cell receptor Immunization Passive Antibodies Monoclonal T lymphocyte Immunotherapy Molecular biology medicine.anatomical_structure Mice Inbred DBA Immunoglobulin G Antibody Formation CD4 Antigens biology.protein Interleukin-2 Tetradecanoylphorbol Acetate Antibody Lymphocyte Culture Test Mixed Baculoviridae HeLa Cells |
| Zdroj: | Clinical immunology (Orlando, Fla.). 119(1) |
| ISSN: | 1521-6616 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect