Modified leukocyte Ig-like receptor family members (LIRs) with increased affinity for class 1 MHC and their uses in modulating T-cell activation

摘要

The present invention provides polypeptides having the property of binding to a given Class I pMHC CHARACTERISED IN THAT said polypeptide has a K_D for the said given Class I pMHC of less than or equal to 1 μM and/or has an off-rate (k_off) for the said given Class I pMHC molecule of 2 S⁻¹ or slower AND said polypeptide has at least a 45% identity and/or 55% similarity to a defined high-affinity ILT-like molecule AND said polypeptide inhibits CD8 binding to the given pMHC to a greater extent than a soluble truncated variant of Wild-Type ILT-2. Such high-affinity ILT-like molecules are useful, either alone or associated with a therapeutic agent, for the inhibition of cytotoxic T cell (CTL) responses.