Abstract: The disclosure provides cysteine substituted immunoglobulins, including polypeptides, antibodies, nucleic acids encoding such polypeptides and antibodies, host cells, vectors and processes for making the same, conjugated derivatives of the antibodies, compositions and methods of making such antibodies and conjugated derivatives, and methods of using the antibodies and conjugated variants for the detection and treatment of cancer and for killing diseased cells. In certain embodiments, the substitution is selected from V266C, G316C, H285C, R301C, V303C, T307C, Y436C and L441C (EU Numbering) or S156 in the hevy chain (under Kabat numbering).