Alessandro Sette

Alessandro Sette is an Italian immunologist. He was born on August 11, 1960, in Rome, Italy, to Pietro Sette, a prominent Italian businessman and politician, and Renata Sette. Sette is a professor at La Jolla Institute for Immunology (LJI). He is an adjunct professor at the University of California, San Diego. Sette studies the specific epitopes that the immune system recognizes in cancer, autoimmunity, allergy, and infectious diseases.[1]

Alessandro Sette
BornAugust 11, 1960 (1960-08-11) (age 63)
Rome, Italy
Alma materUniversity of Rome
Known forDefining how T cells see antigens

In 1988, Sette moved to San Diego to conduct research at San Diego biotech Cytel. He then co-founded Epimmune. In 2003, Sette joined the faculty of La Jolla Institute for Immunology.[2]

Sette co-leads the Immune Epitope Database (IEDB), an NIAID-funded online database that catalogues epitopes involved in immune system recognition of allergens, infectious diseases, autoantigens, and transplanted tissue in humans and various species.

In 2020, Sette published the first study of SARS-CoV-2 epitopes targeted by the human immune system.[3] He has co-led research into CD8+ and CD4+ T cell responses in COVID-19 patients[4] and studied CD8+ T cell cross-reactivity to SARS-CoV-2 epitopes and other coronaviruses.[5]

Education

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.

Publications/patents

Sette is a coauthor of over 900 peer-reviewed publications, and is an inventor on 41 US issued patents. He has a H-factor of 182,[10] and is identified by Clarivate as a highly cited researcher.[11]

Awards and honors
  1. The Scripps Research Institute Adjunct Faculty
  2. American Association of Immunologists Investigator Award (1995)[12]
  3. International Immunomics and Immmunogenics Society Award (2006)[13]
  4. Named as one of the top 400 influential researchers in the last 15 years (2013)
  5. 10th Annual ViE Vaccine Industry Excellence Award (2017)
  6. Fellow, American Association for the Advancement of Science (2020)
  7. Ranked 4th amongst Italian Scientists in Biomedical Sciences (2021)
  8. Honorary Member, Accademia Medica di Roma (2021)
  9. Gold Medal, Italian Society of Internal Medicine (2021)
  10. Fellow, Sigma Xi The Scientific Research Honor Society (2021)
  11. Boulle-SEI International Award (Alicante, Spain 2021)
  12. Fellow, American Academy of Microbiology (2023)[14]
  13. Member, Scientific Council of Italian Scientists & Scholars in North America Foundation, ISSNAF (2023)
  14. Ranked 3rd amongst Italian Scientists in Biomedical Sciences (2023)

Research

In the mid-80s, at the same time as  Paul Allen in Emil Unanue’s lab, Sette together with Soren Buus in Howard Grey’s lab reported the first direct evidence that MHC molecules’ function is to bind antigenic peptides[15][16] and present them to the T cell receptor, which triggers a T cell response. Follow-up work explained MHC restriction.[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.[20][21][22] He discovered and characterized how MHC variants can be grouped according to broad common functional specificities (MHC supertypes), greatly facilitating epitope classification, characterization and understanding the basic rules of epitope-MHC interactions.[23]

Contrary to the then wide-held assumption that T cell receptors (TCR) solely function as on/off switches, Sette showed that depending on the affinity of the interaction, TCR engagement could result in inhibition of T cell activation, normal activation, or heteroclitic stimulation and differential signaling, in a mechanism that is known as TCR antagonism.[24][25] This discovery had a profound influence on the understanding of the impact of epitope analogs on antigen recognition, development of more potent cancer antigens, and basic studies on positive and negative selection.[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.

Sette's group was first to define successful adaptive response to SARS-CoV-2, by studying mild convalescent samples, and defined durability of immune memory in natural infection and vaccination.[34][35] We reported the phenomenon of SARS-CoV-2 preexisting immune memory in unexposed donors, and demonstrated its influence on vaccination outcomes.[36][37] We also demonstrated that T cell responses are largely preserved in terms of recognition of SARS-CoV-2 variants, including Omicron and Delta.[38]

References
  1. "» Sette Lab". www.lji.org. Retrieved January 5, 2021.
  2. Sette, Alessandro (March 28, 2017). "Portrait of an optimist". Human Vaccines & Immunotherapeutics. 13 (6): 1210–1212. doi:10.1080/21645515.2017.1312175. ISSN 2164-5515. PMC 5489282. PMID 28350507.
  3. Grifoni, Alba; Weiskopf, Daniela; Ramirez, Sydney I.; Mateus, Jose; Dan, Jennifer M.; Moderbacher, Carolyn Rydyznski; Rawlings, Stephen A.; Sutherland, Aaron; Premkumar, Lakshmanane; Jadi, Ramesh S.; Marrama, Daniel (June 25, 2020). "Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals". Cell. 181 (7): 1489–1501.e15. doi:10.1016/j.cell.2020.05.015. ISSN 0092-8674. PMC 7237901. PMID 32473127.
  4. Moderbacher, Carolyn Rydyznski; Ramirez, Sydney I.; Dan, Jennifer M.; Grifoni, Alba; Hastie, Kathryn M.; Weiskopf, Daniela; Belanger, Simon; Abbott, Robert K.; Kim, Christina; Choi, Jinyong; Kato, Yu (November 12, 2020). "Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity". Cell. 183 (4): 996–1012.e19. doi:10.1016/j.cell.2020.09.038. ISSN 0092-8674. PMC 7494270. PMID 33010815.
  5. Mateus, Jose; Grifoni, Alba; Tarke, Alison; Sidney, John; Ramirez, Sydney I.; Dan, Jennifer M.; Burger, Zoe C.; Rawlings, Stephen A.; Smith, Davey M.; Phillips, Elizabeth; Mallal, Simon (October 2, 2020). "Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans". Science. 370 (6512): 89–94. Bibcode:2020Sci...370...89M. doi:10.1126/science.abd3871. ISSN 0036-8075. PMC 7574914. PMID 32753554.
  6. Sette, Alessandro; Colizzi, Vittorio; Appella, Ettore; Doria, Gino; Adorini, Luciano (1986). "Analysis of lysozyme-specific immune responses by synthetic peptides. I. Characterization of antibody and T cell-mediated responses to the N-terminal peptide of hen egg-white lysozyme". European Journal of Immunology. 16 (1): 1–6. doi:10.1002/eji.1830160102. PMID 2936608. S2CID 7646979.
  7. Sette, Alessandro; Doria, Gino; Adorini, Luciano (August 1986). "A microcomputer program for hydrophilicity and amphipathicity analysis of protein antigens". Molecular Immunology. 23 (8): 807–810. doi:10.1016/0161-5890(86)90065-9. PMID 2432413.
  8. Buus, S.; Sette, A.; Colon, S. M.; Jenis, D. M.; Grey, H. M. (December 26, 1986). "Isolation and characterization of antigen-Ia complexes involved in T cell recognition". Cell. 47 (6): 1071–1077. doi:10.1016/0092-8674(86)90822-6. ISSN 0092-8674. PMID 3490919. S2CID 53252762.
  9. Sette, A.; Buus, S.; Colon, S.; Smith, J. A.; Miles, C.; Grey, H. M. (July–August 1987). "Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells". Nature. 328 (6129): 395–399. doi:10.1038/328395a0. ISSN 0028-0836. PMID 3497349. S2CID 4266071.
  10. "Alessandro Sette". scholar.google.com. Retrieved February 25, 2023.
  11. "Alessandro Sette's Publons profile".
  12. Sette, Alessandro (March 28, 2017). "Portrait of an optimist". Human Vaccines & Immunotherapeutics. 13 (6): 1210–1212. doi:10.1080/21645515.2017.1312175. ISSN 2164-5515. PMC 5489282. PMID 28350507.
  13. Sette, Alessandro (March 28, 2017). "Portrait of an optimist". Human Vaccines & Immunotherapeutics. 13 (6): 1210–1212. doi:10.1080/21645515.2017.1312175. ISSN 2164-5515. PMC 5489282. PMID 28350507.
  14. "65 Fellows Elected into the American Academy of Microbiology". ASM.org. Retrieved February 25, 2023.
  15. Buus, S.; Sette, A.; Colon, S. M.; Jenis, D. M.; Grey, H. M. (December 26, 1986). "Isolation and characterization of antigen-Ia complexes involved in T cell recognition". Cell. 47 (6): 1071–1077. doi:10.1016/0092-8674(86)90822-6. ISSN 0092-8674. PMID 3490919. S2CID 53252762.
  16. Sette, A.; Buus, S.; Colon, S.; Smith, J. A.; Miles, C.; Grey, H. M. (July–August 1987). "Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells". Nature. 328 (6129): 395–399. doi:10.1038/328395a0. ISSN 0028-0836. PMID 3497349. S2CID 4266071.
  17. Demotz, S.; Grey, H. M.; Sette, A. (August 31, 1990). "The minimal number of class II MHC-antigen complexes needed for T cell activation". Science. 249 (4972): 1028–1030. Bibcode:1990Sci...249.1028D. doi:10.1126/science.2118680. ISSN 0036-8075. PMID 2118680.
  18. Sette, A.; Vitiello, A.; Reherman, B.; Fowler, P.; Nayersina, R.; Kast, W. M.; Melief, C. J.; Oseroff, C.; Yuan, L.; Ruppert, J.; Sidney, J. (December 15, 1994). "The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes". Journal of Immunology. 153 (12): 5586–5592. doi:10.4049/jimmunol.153.12.5586. ISSN 0022-1767. PMID 7527444. S2CID 10660381.
  19. Sette, A.; Buus, S.; Appella, E.; Smith, J. A.; Chesnut, R.; Miles, C.; Colon, S. M.; Grey, H. M. (May 1989). "Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis". Proceedings of the National Academy of Sciences of the United States of America. 86 (9): 3296–3300. Bibcode:1989PNAS...86.3296S. doi:10.1073/pnas.86.9.3296. ISSN 0027-8424. PMC 287118. PMID 2717617.
  20. Peters, Bjoern; Nielsen, Morten; Sette, Alessandro (April 26, 2020). "T Cell Epitope Predictions". Annual Review of Immunology. 38: 123–145. doi:10.1146/annurev-immunol-082119-124838. ISSN 1545-3278. PMID 32045313. S2CID 211085860.
  21. Sette, A.; Buus, S.; Appella, E.; Smith, J. A.; Chesnut, R.; Miles, C.; Colon, S. M.; Grey, H. M. (May 1989). "Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis". Proceedings of the National Academy of Sciences of the United States of America. 86 (9): 3296–3300. Bibcode:1989PNAS...86.3296S. doi:10.1073/pnas.86.9.3296. ISSN 0027-8424. PMC 287118. PMID 2717617.
  22. Ruppert, J.; Sidney, J.; Celis, E.; Kubo, R. T.; Grey, H. M.; Sette, A. (September 10, 1993). "Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules". Cell. 74 (5): 929–937. doi:10.1016/0092-8674(93)90472-3. ISSN 0092-8674. PMID 8104103. S2CID 44308369.
  23. Sette, A.; Sidney, J. (August 1998). "HLA supertypes and supermotifs: a functional perspective on HLA polymorphism". Current Opinion in Immunology. 10 (4): 478–482. doi:10.1016/s0952-7915(98)80124-6. ISSN 0952-7915. PMID 9722926.
  24. De Magistris, M. T.; Alexander, J.; Coggeshall, M.; Altman, A.; Gaeta, F. C.; Grey, H. M.; Sette, A. (February 21, 1992). "Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor". Cell. 68 (4): 625–634. doi:10.1016/0092-8674(92)90139-4. ISSN 0092-8674. PMID 1739971. S2CID 28256727.
  25. Sette, A.; Alexander, J.; Ruppert, J.; Snoke, K.; Franco, A.; Ishioka, G.; Grey, H. M. (1994). "Antigen analogs/MHC complexes as specific T cell receptor antagonists". Annual Review of Immunology. 12: 413–431. doi:10.1146/annurev.iy.12.040194.002213. ISSN 0732-0582. PMID 8011286.
  26. Bertoletti, A.; Sette, A.; Chisari, F. V.; Penna, A.; Levrero, M.; De Carli, M.; Fiaccadori, F.; Ferrari, C. (June 2, 1994). "Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells". Nature. 369 (6479): 407–410. Bibcode:1994Natur.369..407B. doi:10.1038/369407a0. ISSN 0028-0836. PMID 8196768. S2CID 4360736.
  27. Parkhurst, M. R.; Salgaller, M. L.; Southwood, S.; Robbins, P. F.; Sette, A.; Rosenberg, S. A.; Kawakami, Y. (September 15, 1996). "Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues". Journal of Immunology. 157 (6): 2539–2548. doi:10.4049/jimmunol.157.6.2539. ISSN 0022-1767. PMID 8805655. S2CID 20155710.
  28. Dan, Jennifer M.; Mateus, Jose; Kato, Yu; Hastie, Kathryn M.; Yu, Esther Dawen; Faliti, Caterina E.; Grifoni, Alba; Ramirez, Sydney I.; Haupt, Sonya; Frazier, April; Nakao, Catherine (February 5, 2021). "Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection". Science. 371 (6529): eabf4063. doi:10.1126/science.abf4063. ISSN 1095-9203. PMC 7919858. PMID 33408181.
  29. Grifoni, Alba; Weiskopf, Daniela; Ramirez, Sydney I.; Mateus, Jose; Dan, Jennifer M.; Moderbacher, Carolyn Rydyznski; Rawlings, Stephen A.; Sutherland, Aaron; Premkumar, Lakshmanane; Jadi, Ramesh S.; Marrama, Daniel (June 25, 2020). "Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals". Cell. 181 (7): 1489–1501.e15. doi:10.1016/j.cell.2020.05.015. ISSN 0092-8674. PMC 7237901. PMID 32473127.
  30. Lindestam Arlehamn, Cecilia S.; Gerasimova, Anna; Mele, Federico; Henderson, Ryan; Swann, Justine; Greenbaum, Jason A.; Kim, Yohan; Sidney, John; James, Eddie A.; Taplitz, Randy; McKinney, Denise M. (January 2013). "Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset". PLOS Pathogens. 9 (1): e1003130. doi:10.1371/journal.ppat.1003130. ISSN 1553-7374. PMC 3554618. PMID 23358848.
  31. Weiskopf, Daniela; Bangs, Derek J.; Sidney, John; Kolla, Ravi V.; De Silva, Aruna D.; de Silva, Aravinda M.; Crotty, Shane; Peters, Bjoern; Sette, Alessandro (August 4, 2015). "Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity". Proceedings of the National Academy of Sciences of the United States of America. 112 (31): E4256–4263. Bibcode:2015PNAS..112E4256W. doi:10.1073/pnas.1505956112. ISSN 1091-6490. PMC 4534238. PMID 26195744.
  32. Schulten, Véronique; Tripple, Victoria; Sidney, John; Greenbaum, Jason; Frazier, April; Alam, Rafeul; Broide, David; Peters, Bjoern; Sette, Alessandro (November 2014). "Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy". The Journal of Allergy and Clinical Immunology. 134 (5): 1076–1083. doi:10.1016/j.jaci.2014.05.033. ISSN 1097-6825. PMC 4253970. PMID 25042980.
  33. da Silva Antunes, Ricardo; Babor, Mariana; Carpenter, Chelsea; Khalil, Natalie; Cortese, Mario; Mentzer, Alexander J.; Seumois, Grégory; Petro, Christopher D.; Purcell, Lisa A.; Vijayanand, Pandurangan; Crotty, Shane (August 31, 2018). "Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters". The Journal of Clinical Investigation. 128 (9): 3853–3865. doi:10.1172/JCI121309. ISSN 1558-8238. PMC 6118631. PMID 29920186.
  34. Dan, Jennifer M.; Mateus, Jose; Kato, Yu; Hastie, Kathryn M.; Yu, Esther Dawen; Faliti, Caterina E.; Grifoni, Alba; Ramirez, Sydney I.; Haupt, Sonya; Frazier, April; Nakao, Catherine; Rayaprolu, Vamseedhar; Rawlings, Stephen A.; Peters, Bjoern; Krammer, Florian (February 5, 2021). "Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection". Science. 371 (6529): eabf4063. doi:10.1126/science.abf4063. ISSN 1095-9203. PMC 7919858. PMID 33408181.
  35. Goel, Rishi R.; Painter, Mark M.; Apostolidis, Sokratis A.; Mathew, Divij; Meng, Wenzhao; Rosenfeld, Aaron M.; Lundgreen, Kendall A.; Reynaldi, Arnold; Khoury, David S.; Pattekar, Ajinkya; Gouma, Sigrid; Kuri-Cervantes, Leticia; Hicks, Philip; Dysinger, Sarah; Hicks, Amanda (December 3, 2021). "mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern". Science. 374 (6572): abm0829. doi:10.1126/science.abm0829. ISSN 1095-9203. PMC 9284784. PMID 34648302.
  36. Mateus, Jose; Dan, Jennifer M.; Zhang, Zeli; Rydyznski Moderbacher, Carolyn; Lammers, Marshall; Goodwin, Benjamin; Sette, Alessandro; Crotty, Shane; Weiskopf, Daniela (October 22, 2021). "Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells". Science. 374 (6566): eabj9853. doi:10.1126/science.abj9853. ISSN 1095-9203. PMC 8542617. PMID 34519540.
  37. Grifoni, Alba; Weiskopf, Daniela; Ramirez, Sydney I.; Mateus, Jose; Dan, Jennifer M.; Moderbacher, Carolyn Rydyznski; Rawlings, Stephen A.; Sutherland, Aaron; Premkumar, Lakshmanane; Jadi, Ramesh S.; Marrama, Daniel; de Silva, Aravinda M.; Frazier, April; Carlin, Aaron F.; Greenbaum, Jason A. (June 25, 2020). "Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals". Cell. 181 (7): 1489–1501.e15. doi:10.1016/j.cell.2020.05.015. ISSN 0092-8674. PMC 7237901. PMID 32473127.
  38. Gao, Yu; Cai, Curtis; Grifoni, Alba; Müller, Thomas R.; Niessl, Julia; Olofsson, Anna; Humbert, Marion; Hansson, Lotta; Österborg, Anders; Bergman, Peter; Chen, Puran; Olsson, Annika; Sandberg, Johan K.; Weiskopf, Daniela; Price, David A. (March 2022). "Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant". Nature Medicine. 28 (3): 472–476. doi:10.1038/s41591-022-01700-x. ISSN 1546-170X. PMC 8938268. PMID 35042228.
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