CTLA-4/PD-1 Antibodies

Target Information

CTLA4 (Cytotoxic T-Lymphocyte Antigen 4) is a CD28-family receptor expressed on mainly CD4+ T cells. It binds the same ligands as CD28 (CD80 and CD86 on B cells and dendritic cells), but with higher affinity than CD28. However, in contrast to CD28 which enhances cell function when bound at the same time as the T cell receptor, CTLA4 inhibits the T cell and prevents it from functioning. Intracellular CTLA4 is also found in regulatory T cells and may be important to their function.

Cell-mediated immune responses are initiated by T lymphocytes that are themselves stimulated by cognate peptides bound to MHC molecules on antig en-presenting cells (APC). T-cell activation is generally self-limited as activated T cells express receptors such as PD-1 (also known as PDCD-1) that mediate inhibitory signals from the APC. PD-1 can bind two different but related ligands, PDL-1 and PDL-2. Upon binding to either of these ligands, signals generated by PD-1 inhibit the activation of the immune response in the absence of "danger signals" such as LPS or other molecules associated with bacteria or other pathogens. Evidence for this is seen in PD1-null mice who exhibit hyperactivated immune systems and autoimmune diseases. Despite its predicted molecular weight, PD-1 often migrates at higher molecular weight in SDS-PAGE.