GENES ENCODING SINGLE CHAIN HUMAN LEUKOCYTE ANTIGEN E (HLA-E) PROTEINS TO PREVENT NATURAL KILLER CELL-MEDIATED CYTOTOXICITY

摘要

Single chain polypeptide forms of HLA-E useful in manipulating and ascertaining natural killer (NK) cell function are disclosed. The single chain trimer (SCT) form of HLA-E is comprised of the signal peptide from human beta-2 microglobulin (β2m), a canonical HLA-E binding peptide, a fifteen amino acid linker, mature human β2m, a twenty amino acid linker, and mature HLA-E heavy chain. The single chain dimer (SCD) form of HLA-E is comprised of the signal peptide from human β2m, mature human β2m, a twenty amino acid linker, and mature HLA-E heavy chain. The disclosed polypeptides can be used to inhibit NK cell cytotoxicity and cytokine production, enumerate and/or purify NK cell subsets, and identify biologically relevant HLA-E ligands. The disclosed HLA-E SCT and SCD nucleic acid sequences can be used a platform for synthesis of additional biologically active major histocompatibility class I protein single chain trimers and dimers.