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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033614-03
Application #
2068687
Study Section
Immunobiology Study Section (IMB)
Project Start
1993-07-01
Project End
1996-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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
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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

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