Alessandro Sette

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Alessandro Sette
Alessandro-Sette.png
BornAugust 11, 1960 (1960-08-11) (age 64)
Rome, Italy
Alma materUniversity of Rome
Known forDefining how T cells see antigens

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 the 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]

Contents

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 the 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]

Throughout his career, Sette has maintained strong scientific ties with Italy and currently is a Member of the Scientific Council of ISSNAF, a not-for-profit organization whose mission is to connect, empower and celebrate the Italian Intellectual Diaspora in North America. He was recently named as a Member of ISNAFF's Board of Directors. In 2025, Sette was awarded the title of "Cavaliere dell'Ordine al Merito della Repubblica Italiana" in recognition of his contributions to biomedical science and global health.

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)
  15. Cavaliere dell'Ordine al Merito della Repubblica Italiana (2025)

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. Bibcode:1987Natur.328..395S. 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. Bibcode:1987Natur.328..395S. 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. PMC   10878398 . 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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