Sela is known for his research in immunology, particularly for research on synthetic antigens, molecules that trigger the immune system to attack. This work of Sela has led to the discovery of the genetic control of the immune response, as well as to the design of vaccines based on synthetic molecules.

He was among the first who introduced the use of linear and branched synthetic polypeptides as antigens, and this brought about a better understanding of immunological phenomena.

For several decades, Sela was interested in the possibility of fighting the autoimmune disease, experimental allergic encephalomyelitis with synthetic analogs of the molecules in the myelin sheath of the brain which are capable of provoking the disease.

He is probably best known as the co-developer (with Ruth Arnon and Dvora Teitelbaum) of the multiple sclerosis drug copaxone.