Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation

Phage library clones selected by a conformational epitope-recognizing and inhibitory monoclonal antibody may display moieties that mimic a receptor/ligand-like three-dimensional structure. This pseudoreceptor/ligand should be able to bind to natural ligand/receptor molecules. We tested this idea using anti-T cell costimulatory molecule antibodies and successfully isolated phage clones with costimulatory effects on T-cell proliferation. This strategy facilitates the designing of regulatory peptide molecules in the absence of precise information about the structure-function relationships in receptor/ligand interactions.