Mouse CD4 Antibody (clone GK1.5)

Recombinant murinized CD4 antibody for in vivo use

Anti-mCD4-mIgG2a InvivoFit™ is a murinized anti-mouse monoclonal antibody (mAb) featuring the variable region of the previously described anti-mCD4 GK1.5 clone [1]. Using recombinant technology, the original GK1.5 rat IgG2b constant region has been replaced with a murine IgG2a format which mediates potent cytotoxic functions [2].

CD4 is a transmembrane protein primarily expressed on most thymocytes, and highly expressed by the peripheral mature CD4+ T cell population, including T helper (Th) and regulatory T (Treg) cells [3]. Other immune cells, such as monocytes and macrophages also express CD4, albeit to 10- to 20-fold fewer levels compared to T cells [4].

The anti-mCD4 GK1.5 mAb is commonly used for in vivo depletion of the CD4+ T cell population to study the role of this T cell subset in various immune responses, including anti-pathogenic responses, auto-immunity, cancer, or transplantation [5]. Depending on the nature of the experiment, extended treatment schedules (up to several months) may be required. Upon repeated injection of a xenogeneic mAb, mice produce anti–species antibodies, causing the removal of the administered mAb from circulation, thereby considerably reducing treatment efficacy. Moreover, this immunogenicity can lead to fatal hypersensitivity reactions [5-7] which can be reduced by mAb murinization [8].
Anti-mCD4-mIgG2a is provided in an InvivoFit™ grade, a high-quality standard specifically adapted to in vivostudies.
 

Key features of Anti-mCD4-mIgG2a InvivoFit™:

• Derives from the GK1.5 clone, rat IgG2b,κ
• Features the mIgG2a isotype (constant region)
• Filter-sterilized (0.2 µm), endotoxin level < 1 EU/mg
• Suitable for parental delivery in mice (azide-free)
• Low aggregation < 5%
• Produced in animal-free facilities and defined media

Anti-mCD4-mIgG2a InvivoFit™ is produced in Chinese hamster ovary (CHO) cells and purified by affinity chromatography with protein A. The specific binding of this mAb to cell surface mCD4 and its in vivo depleting function have been confirmed (see Figures).

References:

1. Dialynas D.P. et al., 1983. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 74:29-56
2. Nimmerjahn F. & Ravetch J.V., 2005. Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science. 310(5753):1510-2.
3. Zhu J. et al., 2010. Differentiation of effector CD4 T cell populations. Annual Rev Immunol. 28:445-489.
4. Collman R. et al., 1990. Macrophage-tropic strains of human immunodeficiency virus type 1 utilize the CD4 receptor. J Virol. 64(9):4468-76.
5. Laky K. & Kruisbeek A.M., 2016. In vivo depletion of T lymphocytes. Current Protocols Immunology. 4.1.1-4.1.9. doi: 10.1002/0471142735.im0401s113.
6. Mall C. et al., 2016. Repeated PD-1/PD-L1 monoclonal antibody administration induces fatal xenogenic hypersensitivity reactions in a murine model of breast cancer. Onco Immunol. 5(2):e1075114.
7. Murphy, J.T. et al., 2014. Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice. Blood. 123(14):2172-2180.
8. Belmar N.A. et al., 2017. Murinization and H chain isotype matching of Anti-GITR antibody DTA-1 reduces immunogenicity-mediated anaphylaxis in C57BL/6 mice. J Immunol. 198:4502-4512.