A method of preparing an engineered antibody exhibiting pH-dependent binding to its antigen, comprising the steps of: (a) providing a parental antibody which binds to an antigen; (b) preparing a panel of engineered variants of said parental antibody, wherein each of said engineered variants in said panel differs from said parental antibody by substitution of at least one amino acid residue with a histidine residue, wherein at least one amino acid residue selected from the following hot-spot list is substituted with histidine: VH CDR1 H31, H32, H33, H35 VH CDR2 H50, H52, H52a, H53, H56, H58, H59, H62, H63 VH CDR3 H95, H96, H97, H98, H99, H100, H100a, H100b, H100c, H100d, H100e, H100f, H100h, H100i, H100j, H100l, H101, H102 VL CDR1 L27, L27d, L29, L30, L31, L32, L34 VL CDR2 L51, L52, L53, L54, L55 VL CDR3 L89, L90, L91, L92, L93, L94, L95a, L95b, L95c, L96 FR L49, L87 and at least one amino acid residue from the following cold-spot list is not substituted with histidine: VH CDR1 H34, H35a, H35b, H35c VH CDR2 H51, H52b, H52c, H54, H55, H57, H60, H61, H64, H65 VH CDR3 H100g, H100k, H100m, H100n VL CDR1 L24, L25, L26, L27a, L27b, L27c, L27e, L28, L33 VL CDR2 L50, L51a, L51b, L51c, L51d, L56 VL CDR3 L95, L95d, L95e, L95f, L97 wherein the amino acid residues are identified according to the KABAT numbering system; and wherein each of said engineered variants in said panel comprises an Fc region; (c) screening said panel of engineered variants for pH dependent binding to said antigen and thereby identifying an engineered antibody exhibiting pH-dependent binding to said antigen; and wherein said engineered antibody identified in part (c) has lower affinity for its antigen at an acidic pH in the range of pH 5.5 to pH 6.0 than at neutral pH 7.4. (a) providing a parental antibody which binds to an antigen; (b) preparing a panel of engineered variants of said parental antibody, wherein each of said engineered variants in said panel differs from said parental antibody by substitution of at least one amino acid residue with a histidine residue, wherein at least one amino acid residue selected from the following hot-spot list is substituted with histidine: VH CDR1 H31, H32, H33, H35 VH CDR2 H50, H52, H52a, H53, H56, H58, H59, H62, H63 VH CDR3 H95, H96, H97, H98, H99, H100, H100a, H100b, H100c, H100d, H100e, H100f, H100h, H100i, H100j, H100l, H101, H102 VL CDR1 L27, L27d, L29, L30, L31, L32, L34 VL CDR2 L51, L52, L53, L54, L55 VL CDR3 L89, L90, L91, L92, L93, L94, L95a, L95b, L95c, L96 FR L49, L87 and at least one amino acid residue from the following cold-spot list is not substituted with histidine: VH CDR1 H34, H35a, H35b, H35c VH CDR2 H51, H52b, H52c, H54, H55, H57, H60, H61, H64, H65 VH CDR3 H100g, H100k, H100m, H100n VL CDR1 L24, L25, L26, L27a, L27b, L27c, L27e, L28, L33 VL CDR2 L50, L51a, L51b, L51c, L51d, L56 VL CDR3 L95, L95d, L95e, L95f, L97 wherein the amino acid residues are identified according to the KABAT numbering system; and wherein each of said engineered variants in said panel comprises an Fc region; wherein the amino acid residues are identified according to the KABAT numbering system; and wherein each of said engineered variants in said panel comprises an Fc region; (c) screening said panel of engineered variants for pH dependent binding to said antigen and thereby identifying an engineered antibody exhibiting pH-dependent binding to said antigen; and wherein said engineered antibody identified in part (c) has lower affinity for its antigen at an acidic pH in the range of pH 5.5 to pH 6.0 than at neutral pH 7.4. <EOS>