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Yang D Dai, Ph.D.

Assistant Professor Adjunct
Department of Immunology and Microbiology
California Campus
Scripps VIVO Scientific Profile
ydai@scripps.edu
(858) 784-8110

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Self Antigens in T cell-mediated Regulation and Autoimmunity


Introduction:  
Availability of MHC-binding peptides and affinity-dependent T-cell receptor recognition contribute to the effectiveness of adaptive immune responses. First, antigens and peptides that are efficiently presented in thymus will deplete high affinity T cells and induce tolerance. However, there are many self antigens that are either not available in thymus or their peptides are not presented efficiently on antigen presenting cells. These antigens and peptides are not tolerized, and their cognate T cells are the basis of autoimmunity. Second, within a competent T cell repertoire, there are many T cells that can recognize a single peptide with a range of various affinities, possibly also cross-reactive to other similar peptides or peptide-MHC complexes. The effectiveness of an immune response largely depend on the availability of tolerized vs. non-tolerized antigens, as well as the frequencies of high affinity vs. cross-reactive T cells for each peptide.

Projects: Autoimmune triggers of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice
The initial autoimmune trigger or event remains unknown in NOD mice, an animal model for human juvenile T1D. Nevertheless, autoreactive T cells are activated very early (2-3 wk-old) at the pancreas of all NOD mice, suggesting that antigenic trigger(s) arise endogenously in the pancreas. We have recently studied immune responses to one type of secreted microvesicles named exosomes, which are nano-size (30-100nm) membrane structure that are released by cells following fusion of late endosomes and/or multivesicular bodies with plasma membrane. We found that exosomes are strongly pro-inflammatory and contain antigens capable of stimulating autoreactive B and T cells. Interestingly, mesenchymal stem cells from pancreatic islet can release such microvesicles, indicating islet development or regeneration may act as an autoimmune trigger via abnormal/excess exosome secretion. We are in the process of studying candidate exosomal antigens and pathways to break/induce tolerance to exosomes and the antigens.

 

 

 

 

Education

Ph.D., Immunology, Memorial University of Newfoundland, Canada, 2002

Professional Experience

2014-2017 Assistant Professor of IMS, Immunology and Microbial Science (IMS), The Scripps Research Institute
2008-2014 Assistant Member, Torrey Pines Institute for Molecular Studies
2005-2008 Senior Research Scientist, Torrey Pines Institute for Molecular Studies
2002-2005 Postdoctoral Fellow, Torrey Pines Institute for Molecular Studies
2001-2002 Research Fellow, La Jolla Institute for Allergy and Immunology

Selected References

All Publications

1999. Y. Dai, K. Carayanniotis, P. Eliades, P. Lymberi, P. Shepherd, Y-C. Kong and G. Carayanniotis. Enhancing or suppressive effects of antibodies on processing of a pathogenic T-cell epitope in thyroglobulin. J. Immunol. 162: 6987-6992. PMID: 10358139

2002. Y. D. Dai, V. P. Rao and G. Carayanniotis. Enhanced iodination of thyroglobulin facilitates processing and presentation of a cryptic pathogenic peptide J. Immunol.168:5907-5911. PMID: 12023396

2005. Y. D. Dai, P. Eliades, K. A. Carayanniotis, D. J. McCormick, Y. M. Kong, P. Kordopatis, P. Lymberi and G. Carayanniotis. Thyroxine-binding antibodies inhibit T-cell recognition of a pathogenic thyroglobulin epitope. J. Immunol. 174:3105-10. PMID: 15728526

2005. Y. D. Dai, K. P. Jensen, A. Lehuen, E. L. Masteller, J. A. Bluestone, D. B. Wilson, E. E. Sercarz. A peptide of glutamic acid decarboxylase 65 can recruit and expand a diabetogenic T cell clone, BDC2.5, in the pancreas, J. Immunol. 175:3621-3627. PMID: 16148106 

2005. Y. D. Dai, G. Carayanniotis and E. Sercarz. Spreading of autoimmunity via reciprocal activation of autoantigen-specific T and B cells. Cellular & Molecular Immunology 2:169-175. PMID: 1621288

2008. Y. D. Dai, K. P. Jensen, I. Marrero, N. Li, A. Quinn, and E. E. Sercarz. N-terminal flanking residues of a diabetes-associated GAD65 determinant are necessary for activation of antigen-specific T cells in diabetes-resistant mice. Eur. J. Immunol. 38:968-76. PMID: 18395850

2009. Y. D. Dai, I. Marrero, P. Gros, H. Zaghouani, L. S. Wicker and E. E. Sercarz. Slc11a1 (formerly Nramp1) enhances the autoimmune diabetogenic T-cell response by altering processing and presentation of pancreatic islet antigens. Diabetes 58:156-164. PMID: 18984740

2011. H. Sheng, S. Hassanali, C. Nugent, L. Wen, E. Hamilton-Williams, P. Dias, and Y.D. Dai. Insulinoma-released exosomes or microparticles are immunostimulatory and can activate autoreactive T cells spontaneously developed in non-obese diabetic mice. J. Immunol. 187(4):1591-600. PMID: 21734072

2012. I. Marrero, A. Vong, Y. Dai, and J. D. Davies. T cell populations in the pancreatic lymph node naturally and consistently expand and contract in NOD mice as disease progresses. Mol Immunol. 52(1):9-18. PMID: 22580347

2013. X. Lin, E.E. Hamilton-Williams, D. B. Rainbow, K. M. Hunter, Y. D. Dai, J. Cheung, L. B. Peterson, L. S. Wicker, L. A. Sherman. Genetic Interactions among Idd3, Idd5.1, Idd5.2, and          Idd5.3 Protective Loci in the Nonobese Diabetic Mouse Model of Type 1 Diabetes. J. Immunol. 190(7):3109-20. PMID: 23427248

2013. R. Bashratyan, H. Sheng, D. Regn, M. J. Rahman, and Y D. Dai. Insulinoma-released exosomes activate autoreactive marginal zone-like B cells that expand endogenously in prediabetic NOD mice. Eur. J. Immunol. 43(10):2588-97. PMID: 23817982

2014. M.J. Rahman, D. Regn, R. Bashratyan and Y.D. Dai. Exosomes released by islet-derived mesenchymal stem cells trigger autoimmune responses in NOD mice. Diabetes 63(3):1008-20. PMID: 24170696