Abstract

The immune response to insulin provides a model system that is unique among well-studied antigens. The long-term objective of this study is to exploit novel aspects of this immune response to gain a deeper understanding of the cellular and molecular mechanisms responsible for regulating the magnitude and specificity of immune responses to insulin and other antigens. Major T cell determinants in insulin are generated during antigen processing by reduction of disulfide bonds with no requirement for proteolytic cleavage.
The first aim i s to characterize immunodominant T cell determinants in insulin recognized by mouse and human T cells using functional assays and biochemical techniques. Emphasis is placed on defining the role of cysteine thiol groups in antigen processing and T cell recognition.
The second aim i s focused on analysis of the effect of MHC polymorphism on the magnitude and specificity of the immune response to insulin.
The third aim i s to characterize a second peptide-binding site in class II MHC that may be used to present insulin B chain peptides and other antigens to a subset of T cells. The functional significance of alternative pathways for antigen presentation and the potential relationship with superantigen presentation will be explored. It is expected that the proposed study will broaden our general understanding of how antigen processing events, self tolerance, and MHC polymorphism affect the specificity and magnitude of immune responses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI033614-01A1
Application #
3148689
Study Section
Immunobiology Study Section (IMB)
Project Start
1993-07-01
Project End
1996-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Zhou, Zemin; Reyes-Vargas, Eduardo; Escobar, Hernando et al. (2017) Peptidomic analysis of type 1 diabetes associated HLA-DQ molecules and the impact of HLA-DM on peptide repertoire editing. Eur J Immunol 47:314-326
Zhou, Zemin; Reyes-Vargas, Eduardo; Escobar, Hernando et al. (2016) Type 1 diabetes associated HLA-DQ2 and DQ8 molecules are relatively resistant to HLA-DM mediated release of invariant chain-derived CLIP peptides. Eur J Immunol 46:834-45
Chen, Lili; Reyes-Vargas, Eduardo; Dai, Hu et al. (2014) Expression of the mouse MHC class Ib H2-T11 gene product, a paralog of H2-T23 (Qa-1) with shared peptide-binding specificity. J Immunol 193:1427-39
Gu, Yapeng; Jensen, Peter E; Chen, Xinjian (2013) Immunodeficiency and autoimmunity in H2-O-deficient mice. J Immunol 190:126-37
Chen, Lili; Jay, David C; Fairbanks, Jared D et al. (2011) An MHC class Ib-restricted CD8+ T cell response to lymphocytic choriomeningitis virus. J Immunol 187:6463-72
Zhou, Zemin; Callaway, Kari A; Weber, Dominique A et al. (2009) Cutting edge: HLA-DM functions through a mechanism that does not require specific conserved hydrogen bonds in class II MHC-peptide complexes. J Immunol 183:4187-91
Swanson 2nd, Phillip A; Pack, Christopher D; Hadley, Annette et al. (2008) An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. J Exp Med 205:1647-57
Escobar, Hernando; Crockett, David K; Reyes-Vargas, Eduardo et al. (2008) Large scale mass spectrometric profiling of peptides eluted from HLA molecules reveals N-terminal-extended peptide motifs. J Immunol 181:4874-82
Jay, David C; Reed-Loisel, Lisa M; Jensen, Peter E (2008) Polyclonal MHC Ib-restricted CD8+ T cells undergo homeostatic expansion in the absence of conventional MHC-restricted T cells. J Immunol 180:2805-14
Chen, Xinjian; Reed-Loisel, Lisa M; Karlsson, Lars et al. (2006) H2-O expression in primary dendritic cells. J Immunol 176:3548-56

Showing the most recent 10 out of 39 publications