CTLA-4 [CD152] – CD80 – CD86 – CD28 Network

Cytotoxic T lymphocyte antigen 4 (CTLA-4; CD152) is an immune checkpoint receptor expressed on the surface of activated T cells. During immune response, T cell activation is initiated when an antigen is presented to the T cell receptor (TCR) by the major histocompatibility complex (MHC) on antigen-presenting cells (APCs). Antigen presentation alone, however, is not sufficient to induce an immune response. Completing the activation process requires a second signal. To maintain activation of an immune response, the primary costimulatory receptor on T cells CD28 binds to the ligands CD80 (B7-1) and CD86 (B7-2) on APCs. When CTLA-4 is upregulated, it competes with CD28 and has a greater affinity for CD80/86. Binding of CTLA-4 to CD80/86 inhibits T cell activation, preserving balance when the immune system is overactive.

CTLA-4 can also be found on regulatory T cells (Tregs), where it is a key driver of their ability to suppress T cell activity. With an almost indefinite lifespan, memory T cells provide long-term immunity. After they have been exposed to tumor antigen, memory T cells immediately mount an immune response against the tumor. The presence of memory T cells is associated with long-term survival and low risk of tumor recurrence in cancer. Tumor cells utilize the CTLA-4 pathway to suppress initiation of an immune response, resulting in decreased T cell activation and a reduced ability to proliferate into memory T cells. Targeting CTLA-4 can restore an immune response through the increased accumulation, function and survival of T cells and memory T cells, as well as the depletion of Tregs, and consequently improve the antitumor response.

LIT:  CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition: E.I. Buchbinder & A. Desai; Am. J. Clin. Oncol. 39, 98 (2016) • CTLA-4: a moving target in immunotherapy: B. Rowshanravan, et al.; Blood 131, 58 (2018) • Evolving Roles for Targeting CTLA-4 in Cancer Immunotherapy: Y. Zhao, et al.; Cell Physiol. Biochem. 47, 721 (2018)

Biologically Active CTLA-4, CD80, CD86 and CD28 Proteins  

VALIDATED Antibodies for CTLA-4, CD80, CD86 and CD28 Research

Select Your Pathway of Interest  & Discover High Quality Reagents