Cell-mediated immune responses are initiated by T lymphocytes that are themselves stimulated by cognate peptides bound to MHC molecules on presenting cells (APC). T-cell activation is generally self-limited as activated T cells express receptors such as PDCD-1 that mediate inhibitory signals from the APC. PDCD-1 can bind two different but related ligands, PDL-1 and PDL-2. Upon binding to either of these ligands, signals generated by PDCD1 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 PDCD1-null mice who exhibit hyperactivated immune systems and autoimmune diseases. Despite its predicted molecular weight, PDCD1 often migrates at higher molecular weight in SDS-PAGE.