Do we all have type 1 diabetes? Revisiting the pre-clinical phase of disease

Luc TEYTON (Scripps Research Institute, La Jolla, CA, USA)

05 December 2022


Pratical info

12:00 - 13:00
Reduced mobility access

Research Overview:

The laboratory of L. Teyton is trying to elucidate the molecular mechanisms by which the ligation of the T cell receptor to its ligand, an MHC-peptide complex, activates T cells. Similar studies are carried out on TCR/pMHC pairs involved in autoimmune diseases with two goals. First, identify self-peptides involved in autoimmunity. Secondly, measure the affinity of self MHC-self pMHC complexes and determine if pathogenic T cells arise from escaping negative selection or breakage of peripheral tolerance. The corollary question is to determine if autoimmunity is a deviance of a normal immune response or the innate property of a T cell response against a self-antigen. The answers to these questions will be determinant in choosing new therapeutic strategies.

Selected publications

Sharma S, Pettus J, Gottschalk M, Abe B, Gottlieb P, Teyton L. Single-Cell Analysis of CD4 T Cells in Type 1 Diabetes: From Mouse to Man, How to Perform Mechanistic Studies. Diabetes. 2019 Oct;68(10):1886-1891. doi: 10.2337/dbi18-0064. PMID: 31540941; PMCID: PMC6754240.

Gioia L, Holt M, Costanzo A, Sharma S, Abe B, Kain L, Nakayama M, Wan X, Su A, Mathews C, Chen YG, Unanue E, Teyton L. Position β57 of I-Ag7 controls early anti-insulin responses in NOD mice, linking an MHC susceptibility allele to type 1 diabetes onset. Sci Immunol. 2019 Aug 30;4(38):eaaw6329. doi:10.1126/sciimmunol.aaw6329. PMID: 31471352; PMCID: PMC6816460.

Holt M, Costanzo A, Gioia L, Abe B, Su AI, Teyton L. Gene Profiling and T Cell Receptor Sequencing from Antigen-Specific CD4 T Cells. Methods Mol Biol. 2018;1712:217-238. doi: 10.1007/978-1-4939-7514-3_14. PMID: 29224077.

Lantz O, Teyton L. Identification of T cell antigens in the 21st century, as difficult as ever. Semin Immunol. 2022 Sep 29;60:101659. doi:10.1016/j.smim.2022.101659. Epub ahead of print. PMID: 36183497.

Martens PJ, Ellis D, Bruggeman Y, Viaene M, Laureys J, Teyton L, Mathieu C, Gysemans C. Preventing type 1 diabetes in late-stage pre-diabetic NOD mice with insulin: A central role for alum as adjuvant. Front Endocrinol (Lausanne). 2022 Oct 20;13:1023264. doi: 10.3389/fendo.2022.1023264. PMID: 36339431; PMCID: PMC9630573.

Polonskaya Z, Deng S, Sarkar A, Kain L, Comellas-Aragones M, McKay CS, Kaczanowska K, Holt M, McBride R, Palomo V, Self KM, Taylor S, Irimia A, Mehta SR, Dan JM, Brigger M, Crotty S, Schoenberger SP, Paulson JC, Wilson IA, Savage PB, Finn MG, Teyton L. T cells control the generation of nanomolar-affinity anti-glycan antibodies. J Clin Invest. 2017 Apr 3;127(4):1491-1504. doi: 10.1172/JCI91192. Epub 2017 Mar 13. PMID: 28287405; PMCID: PMC5373877.

Boudinot P, Mondot S, Jouneau L, Teyton L, Lefranc MP, Lantz O. Restricting nonclassical MHC genes coevolve with TRAV genes used by innate-like T cells in mammals. Proc Natl Acad Sci U S A. 2016 May 24;113(21):E2983-92. doi: 10.1073/pnas.1600674113. Epub 2016 May 11. PMID: 27170188; PMCID: PMC4889381.

Kain L, Webb B, Anderson BL, Deng S, Holt M, Costanzo A, Zhao M, Self K, Teyton A, Everett C, Kronenberg M, Zajonc DM, Bendelac A, Savage PB, Teyton L. The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides. Immunity. 2014 Oct 16;41(4):543-54. doi: 10.1016/j.immuni.2014.08.017. Erratum in: Immunity. 2014 Nov 20;41(5):867. Constanzo, Anne [corrected to Costanzo, Anne]. PMID: 25367571; PMCID: PMC4220304.

Müller-Calleja N, Hollerbach A, Royce J, Ritter S, Pedrosa D, Madhusudhan T, Teifel S, Meineck M, Häuser F, Canisius A, Nguyen TS, Braun J, Bruns K, Etzold A, Zechner U, Strand S, Radsak M, Strand D, Gu JM, Weinmann-Menke J, Esmon CT, Teyton L, Lackner KJ, Ruf W. Lipid presentation by the protein C receptor links coagulation with autoimmunity. Science. 2021 Mar 12;371(6534):eabc0956. doi: 10.1126/science.abc0956. PMID: 33707237; PMCID: PMC9014225.

Cook DP, Cunha JPMCM, Martens PJ, Sassi G, Mancarella F, Ventriglia G, Sebastiani G, Vanherwegen AS, Atkinson MA, Van Huynegem K, Steidler L, Caluwaerts S, Rottiers P, Teyton L, Dotta F, Gysemans C, Mathieu C. Intestinal Delivery of Proinsulin and IL-10 via Lactococcus lactis Combined With Low-Dose Anti-CD3 Restores Tolerance Outside the Window of Acute Type 1 Diabetes Diagnosis. Front Immunol. 2020 Jun 9;11:1103. doi: 10.3389/fimmu.2020.01103. PMID: 32582188; PMCID: PMC7295939.

Srivastava N, Hu H, Vomund AN, Peterson OJ, Baker RL, Haskins K, Teyton L, Wan X, Unanue ER. Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms. Diabetes. 2021 Dec;70(12):2860-2870. doi: 10.2337/db21 0513. Epub 2021 Sep 8. PMID: 34497137; PMCID: PMC8660984.

Sharma S, Gioia L, Abe B, Holt M, Costanzo A, Kain L, Su A, Teyton L. Using single cell analysis for translational studies in immune mediated diseases: Opportunities and challenges. Mol Immunol. 2018 Nov;103:191-199. doi: 10.1016/j.molimm.2018.09.020. Epub 2018 Oct 6. Erratum in: Mol Immunol. 2019 Mar;107:165. PMID: 30300798; PMCID: PMC6258053.

Ito Y, Ashenberg O, Pyrdol J, Luoma AM, Rozenblatt-Rosen O, Hofree M, Christian E, Ferrari de Andrade L, Tay RE, Teyton L, Regev A, Dougan SK, Wucherpfennig KW. Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity. J Exp Med. 2018 Oct 1;215(10):2617-2635. doi: 10.1084/jem.20180300. Epub 2018 Sep 5. PMID: 30185635; PMCID: PMC6170167.

Benlagha K, Kyin T, Beavis A, Teyton L, Bendelac A. A thymic precursor to the NK T cell lineage. Science. 2002 Apr 19;296(5567):553-5. doi: 10.1126/science.1069017. PMID: 11968185.

Homann D, Teyton L, Oldstone MB. Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory. Nat Med. 2001 Aug;7(8):913-9. doi: 10.1038/90950. PMID: 11479623.

Corper AL, Stratmann T, Apostolopoulos V, Scott CA, Garcia KC, Kang AS, Wilson IA, Teyton L. A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science. 2000 Apr 21;288(5465):505-11. doi: 10.1126/science.288.5465.505. PMID: 10775108.

Garcia KC, Teyton L, Wilson IA. Structural basis of T cell recognition. Annu Rev Immunol. 1999;17:369-97. doi: 10.1146/annurev.immunol.17.1.369. PMID: 10358763.