Blockade of T Cell Activation Using a Surface-Linked Single-Chain Antibody to CTLA-4 (CD152)

摘要: CTLA-4 (CD152) engagement can down-regulate T cell activation and promote the induction of immune tolerance. However, strategy attenuating by engaging has been limited sharing its natural ligands with costimulatory protein CD28. In present study, a CTLA-4-specific single-chain Ab (scFv) was developed expressed on surface to selective this regulatory molecule. Transfectants expressing anti-CTLA-4 scFv at their bound soluble but not Coexpression anti-CD3epsilon anti-CD28 scFvs artificial APCs reduced proliferation IL-2 production resting preactivated bulk cells as well CD4+ CD8+ subsets. Importantly, expression same TCR ligand essential for inhibitory effects ligation. CTLA-4-mediated inhibition tyrosine phosphorylation components proximal signaling apparatus similarly dependent coexpression surface. These findings support predominant role function in modification signal. Using from DO11.10 2C transgenic mice, negative ligation were also demonstrated during stimulation Ag-specific MHC/peptide complexes. Together these studies demonstrate that using membrane-bound results attenuated responses only when coengaged cell/APC interaction define an approach harnessing immunomodulatory potential