A CTLA-4 nanobody improves the immunity of mice against challenges with Staphylococcus aureus and Streptococcus agalactiae

Abstract

Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), also known as CD152, is a transmembrane receptor and leukocyte differentiation antigen on T cells that participates in the negative regulation of immune responses. CTLA-4 Ig can effectively and specifically inhibit cellular and humoral immune responses in vivo and in vitro, and is therefore, considered to be a promising new immunosuppressive antibody. In this study, we investigated the role of CTLA-4 nanobody in immunity. We purified recombinant CTLA-4 protein and constructed a phage display nanobody library. After screening the library, we obtained a nanobody with high affinity for the CTLA-4 protein. The nanobody was expressed and purified and the specific high-affinity for CTLA-4 confirmed by enzyme-linked immunosorbent assay. The nanobody was shown to enhance the activity and nitric oxide (NO) production of bone marrow derived dendritic cells (DCs) as well as their ability to capture foot-and-mouth disease virus (FMDV). The CTLA-4 nanobody also improved the immunity of animals after challenge with Staphylococcus aureus and Streptococcus agalactiae, thus indicating the potential of the CTLA-4 nanobody to improve cellular immunity and enhance immune responses.