Abstract: Recombinant monoclonal antibodies (mAbs) and fragments that bind specifically to an HLA-E-peptide complex, including HLA-E-VL9 complexes, and regulate the cytotoxicity effector cell function of NK and/or CD8+ T-cells positive for cell-surface expression of NKG2A (“NKG2A+”). Herein, monoclonal antibodies were recombinantly derived from isolated functional HLA-E-VL9-specific mAbs from HLA-E-VL9 peptide-immunized HLA-B transgenic mice and from the naive human B cell repertoire. Such antibodies are capable of regulating effector cell cytotoxicity and can preferentially recognize HLA-E-VL9 peptide complexes expressed on the surface of tumor cells. The invention provides methods for using HLA-E-VL9 m Abs to modulate NK and/or CD8+ T-cell function as part of immunotherapeutic strategies.

Abstract: The present invention provides affinity matured recombinant monoclonal antibodies (mAbs) and fragments that bind specifically to an HLA-E-peptide complex, including HLA-E-VL9 complexes, and. regulate the cytotoxicity effector cell function of NK and/or CD8+ T-cells positive for cell-surface expression of NKG2A (“NKG2A+”). Herein, monoclonal antibodies were recombinant.lv derived from isolated functional HLA-E-VL9-specific mAbs from HLA-E-VL9 peptide-immunized HLA-B transgenic mice and from the naive human B cell repertoire. Such antibodies are capable of regulating effector cell cytotoxicity' and can preferentially recognize HLA-E-VL9 peptide complexes expressed on the surface of tumor cells. The monoclonal antibodies were subject to one or more rounds of affinity 7 maturation. The invention provides methods for using affinity matured HLA-E-VL9 mAbs to modulate NK and/or CD8+T-cell function as part of immunotherapeutic strategies.