A multi-transmembrane protein antigen includes a polypeptide corresponding to an extracellular loop of the multi-transmembrane protein, the N-terminal and C-terminal of the polypeptide being fixed on a solid substrate or the N-terminal and C-terminal being attached to both ends of a linker to form a cyclic structure, an antibody specifically binding to the antigen or an antigen-binding fragment thereof, and a method for screening an antibody specifically binding to the antigen. The present invention may be usefully employed for effective production of antibodies for multi-transmembrane proteins that play important roles in disease-related phenomena such as cell signaling.