In the late 1980s, Dr. Linsley was working at Oncogen (later bought by Bristol-Meyers Squibb) where he was conducting research on a project to identify a ligand for CD28, with the hypothesis that that molecule might trigger T cell activation. He found the B7 molecule, showed that it was expressed on activated B cells, bound CD28, and co-stimulated T cell activation. Linsley went on to investigate the newly cloned molecule CLTA-4, which had a similar structure to CD28. He found that CTLA-4 also bound B7 and that it bound B7 more strongly than CD28. The discovery of these interactions between B cell bound B7 and T cell molecules CD28 and CTLA-4 helped demonstrate that interactions between B and T cells were involved in immune response regulation.
Dr. Linsley continued investigating CTLA-4 as a potential immunosuppressant and went on to develop the drug Orencia, which is composed of a portion of the CTLA-4 protein that binds B7 and blocks T cell activation. Orencia was approved for use in rheumatoid arthritis by the FDA in 2005 and for use in active psoriatic arthritis in 2017.