Methods and compositions for identifying peptide modulators of cell surface receptors

A method of screening, comprising:

• assaying a population of cells each cell of said population comprising:
• a recombinant nucleic acid encoding a first polypeptide modified for intracellular presentation;
• a recombinant nucleic acid encoding a binding partner for said first polypeptide;
• and,
• a recombinant nucleic acid encoding a test polypeptide;
• said assaying being for identification of a test polypeptide that modulates binding between said first polypeptide and said binding partner.

A method for identifying a cell producing a biologically active polypeptide, comprising:

• lysing samples of cells from pools of cells to make cell lysates;
• assaying a plurality of pools of different lysed cells, the lysed cells of each pool producing a plurality of different conformationally restricted test polypeptides, thereby identifying a pool of cells producing a biologically active conformationally restrained test polypeptide;
• separating the cells in said identified pool;
• and assaying said isolated cells to identify a cell producing said biologically active conformationally restricted test polypeptide.