Helper T lymphocytes play a central role in regulating immune responses. These cells specifically recognize antigen-derived peptides that are stably bound to class Il histocompatibility molecules (MHC) expressed on the surface of specialized antigen presenting cells (APC). The long-term objective of this project is to define the intracellular events and cofactors in APC that regulate the formation of peptide/MHC complexes. The first specific aim of the project is to determine how variation in the pH of intracellular compartments regulates peptide binding by mouse and human MHC molecules. Biochemical and mutational studies will be done to identify structural features of MHC that are responsible for this regulation. The 2nd specific aim is to identify other co-factors that facilitate peptide binding by MHC. Membrane reconstitution experiments will be used to define conditions necessary for efficient peptide binding by cell surface MHC and intracellular oligomers containing MHC and invariant chain. The 3d specific aim is to define mechanisms responsible for unfolding antigen and generation of the peptides that ultimately become associated with MHC. These mechanisms significantly influence the selection of antigenic determinants that become available for recognition by T cells. It is expected that the proposed study will broaden our understanding of critical events that are required for the initiation of protective immunity to infectious agents as well as deleterious responses to self antigens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI030554-08
Application #
2672035
Study Section
Experimental Immunology Study Section (EI)
Project Start
1991-07-01
Project End
1999-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
8
Fiscal Year
1998
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
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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
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