Research Area
1) INFECTIOUS DISEASE: Using T cell epitopes to define immune signatures with productive/protective immunity versus dysfunctional/pathological immunity following natural infection and vaccination against diseases that are relevant to global health, including SARS-CoV-2, Dengue, Zika, Chikungunya, mpox, malaria, M. tuberculosis, B. pertussis, and shingles. 2) ALLERGIES: Identifying T cell epitopes that trigger the inflammatory response to allergens including cockroach, mouse, seasonal and food allergies 3) NEURODEGENERATIVE DISEASE: Characterizing autoimmune features in patients with Parkinson’s Disease and animal models to bring about new means to diagnose and treat neurodegenerative disease. 4) GLOBAL RESOURCES: Directing the national Immune Epitope Database (IEDB), which catalogs all epitopes for humans, non-human primates, rodents, and other vertebrates, from allergens, infectious diseases, autoantigens and transplants, as well as CEDAR, which does the same for cancer
Team Description
The success of the Sette Lab is driven by a fearless team of immunologists, bioinformaticians, software developers, curators and data geeks, who are inspired by La Jolla Institute for Immunology’s motto of imagining Life Without Disease. They firmly believe that data is the new currency in research and that large scale data sharing in freely accessible databases powers innovation.
Team Members
Team Show
Publications
Select publications:
Immune Epitope Database:
a. Peters B, Sidney J, Bourne P, Bui HH, Buus S, Doh G, Fleri W, Kronenberg M, Kubo R, Lund O, Nemazee D, Ponomarenko JV, Sathiamurthy M, Schoenberger S, Stewart S, Surko P, Way S, Wilson S, Sette A. The immune epitope database and analysis resource: from vision to blueprint. PLoS Biol. 2005 Mar;3(3):e91. PMCID: PMC1065705
b. Martini S, Nielsen M, Peters B, Sette A. The Immune Epitope Database and Analysis Resource Program 2003–2018: reflections and outlook. Immunogenetics. 2020;72(1):57-76. PMCID: PMC6970984
c. Dhanda SK, Mahajan S, Paul S, Yan Z, Kim H, Jespersen MC, Jurtz V, Andreatta M, Greenbaum JA, Marcatili P, Sette A, Nielsen M, Peters B. IEDB-AR: immune epitope database-analysis resource in 2019. Nucleic Acids Res. 2019 Jul 2;47(W1):W502-6. PMCID: PMC6602498
d. Vita R, Mahajan S, Overton JA, Dhanda SK, Martini S, Cantrell JR, Wheeler DK, Sette A, Peters B. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-43. PMCID: PMC6324067
Understanding immunity and immunopathology in specific disease systems:
a. Lindestam Arlehamn CS, Gerasimova A, Mele F, Henderson R, Swann J, Greenbaum JA, Kim Y, Sidney J, James EA, Taplitz R, McKinney DM, Kwok WW, Grey H, Sallusto F, Peters B, Sette A. Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset. PLoS Pathog. 2013 Jan;9(1):e1003130. PMCID: PMC3554618
b. Weiskopf D, Bangs DJ, Sidney J, Kolla RV, De Silva AD, de Silva AM, Crotty S, Peters B, Sette A. Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31). PMCID: PMC4534238
c. da Silva Antunes R, Babor M, Carpenter C, Khalil N, Cortese M, Mentzer AJ, Seumois G, Petro CD, Purcell LA, Vijayanand P, Crotty S, Pulendran B, Peters B, Sette A. Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters. J Clin Invest. 2018 Aug 31;128(9):3853-3865. doi: 10.1172/JCI121309. Epub 2018 Aug 6. PMID: 29920186; PMCID: PMC6118631.
d. Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, Liong C, McMurtrey C, Hildebrand WH, Mao X, Dawson VL, Dawson TM, Oseroff C, Pham J, Sidney J, Dillon MB, Carpenter C, Weiskopf D, Phillips E, Mallal S, Peters B, Frazier A, Lindestam Arlehamn CS, Sette A. T cells from patients with Parkinson's disease recognize α-synuclein peptides. Nature. 2017 Jun 29;546(7660):656-61. Epub 2017 Jun 21. Erratum in: Nature. 2017 Sep 13;549(7671):292. PMCID: PMC5626019
e)Dhanwani R, Lima-Junior JR, Sethi A, Pham J, Williams G, Frazier A, Xu Y, Amara AW, Standaert DG, Goldman JG, Litvan I, Alcalay RN, Peters B, Sulzer D, Arlehamn CSL, Sette A. Transcriptional analysis of peripheral memory T cells reveals Parkinson's disease-specific gene signatures. NPJ Parkinsons Dis. 2022 Mar 21;8(1):30. doi: 10.1038/s41531-022-00282-2. PMID: 35314697; PMCID:
PMC8938520.
f)Lindestam Arlehamn CS, Dhanwani R, Pham J, Kuan R, Frazier A, Rezende Dutra J, Phillips E, Mallal S, Roederer M, Marder KS, Amara AW, Standaert DG, Goldman JG, Litvan I, Peters B, Sulzer D, Sette A. α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson's disease. Nat Commun. 2020 Apr 20;11(1):1875. doi: 10.1038/s41467-020-15626-w. PMID: 32313102; PMCID: PMC7171193.
Mechanistic studies:
a.De Magistris MT, Alexander J, Coggeshall M, Altman A, Gaeta FC, Grey HM, Sette A. Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. Cell. 1992 Feb 21;68(4):625-34. PMID: 1739971.
b. Sette A, Alexander J, Ruppert J, Snoke K, Franco A, Ishioka G, Grey HM. Antigen analogs/MHC complexes as specific T cell receptor antagonists. Annu Rev Immunol. 1994;12:413-31. Review. PMID: 8011286.
c. Bertoletti A, Sette A, Chisari FV, Penna A, Levrero M, De Carli M, Fiaccadori F, Ferrari C. Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature. 1994 Jun 2;369(6479):407-10. PMID: 8196768.
d. Parkhurst MR, Salgaller ML, Southwood S, Robbins PF, Sette A, Rosenberg SA, Kawakami Y. Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. J Immunol. 1996 Sep 15;157(6):2539-48. PMID: 8805655.
e. Peters B, Nielsen M, Sette A. T cell epitope predictions. Annu Rev Immunol. 2020 Apr 26;38:123-45. PMID: 32045313.
f. Sette A, Buus S, Appella E, Smith JA, Chesnut R, Miles C, Colon SM, Grey HM. Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis. Proc Natl Acad Sci U S A. 1989 May;86(9):3296-300. PMCID: PMC287118
g. Ruppert J, Sidney J, Celis E, Kubo RT, Grey HM, Sette A. Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell. 1993 Sep 10;74(5):929-37. PMID: 8104103
h. Sette A, Sidney J. HLA supertypes and supermotifs: a functional perspective on HLA polymorphism. Curr Opin Immunol. 1998 Aug;10(4):478-82. PMID: 9722926
i. Buus S, Sette A, Colon SM, Jenis DM, Grey HM. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell. 1986 Dec 26;47(6):1071-7. PMID: 3490919
j. Sette A, Buus S, Colon S, Smith JA, Miles C, Grey HM. Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. Nature. 1987 Jul 30-Aug 5;328(6129):395-9. PMID: 3497349.
k. Demotz S, Grey HM, Sette A. The minimal number of class II MHC-antigen complexes needed for T cell activation. Science. 1990 Aug 31;249(4972):1028-30. PMID: 2118680
l. Sette A, Vitiello A, Reherman B, Fowler P, Nayersina R, Kast WM, Melief CJ, Oseroff C, Yuan L, Ruppert J, Sidney J, del Guercio MF, Southwood S, Kubo RT, Chesnut RW, Grey HM, Chisari FV. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol. 1994 Dec 15;153(12):5586-92. PMID: 7527444
Complete List of Published Work in MyBibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/alessandro.sette.1/bibliography/40968398/public/?sort=date&direction=ascending