Sette studies the specific epitopes that the immune system recognizes in cancer, autoimmunity, allergy, and infectious diseases.

[5] Sette received his Laurea in Biological Sciences from the University of Rome, Italy, followed by postdoctoral fellowships in Immunology with Luciano Adorini[6][7] at the C.R.E.

Casaccia in Rome, Italy, and Howard Grey[8][9] at the National Jewish Center for Immunology and Respiratory Medicine in Denver, Colorado.

[17][18] In 1989, utilizing an Apple IIe, Sette wrote the first algorithm[19] to predict peptide binding to two murine MHC alleles and over the course of the next 25 years, he defined motifs associated with over one hundred different class I and class II MHC variants expressed in humans, chimps, macaques, gorilla, horse, and mice.

[26][27] Sette is using epitopes as specific probes to define the understanding of immune responses to many different targets, from infectious diseases such as COVID-19,[28][29] tuberculosis,[30] whooping cough, dengue[31] or Zika, to allergies and asthma caused by pollens,[32] cockroaches and dust mites, to vaccines,[33] autoimmunity and neurodegenerative diseases and cancer.