The present invention relates to a method for generating immunoglobulin sequences against 
cell-associated antigens, more particularly, antigens that are membrane-anchored. The invention also provides immunoglobulin sequences obtainable by the method of the invention. Specifically, the present invention relates to the generation of immunoglobulin sequences by use of 
DNA vaccination. More specifically, the present invention relates to generation of immunoglobulin sequences in camelids, preferably directed against 
cell-associated antigens, in particular antigens with multiple transmembrane spanning domains, including GPCRs and 
ion channels, by 
DNA vaccination. Furthermore, the present invention relates to said immunoglobulin sequences against 
cell-associated antigens, more particularly, antigens that are membrane-anchored, such as e.g. GPCRs and 
ion channels, more preferably 
ion channels.