Abstract

The study of antigen-specific, MHC restricted T cell interactions has been a major focus of our laboratory. This project addresses three aspects of MHC restricted antigen-presentation to T lymphocytes. 1. The nature of processed antigens and their membrane display on antigen-presenting cells. 2. The manipulation of antigens and antigen-presentation to increase immunogenicity. 3. The role of non-MHC encoded structures in antigen- presentation and cell-cell interaction. These issues will be investigated with defined antigens both in vivo and in vitro, the latter with transformed clones of functional specific T cells in conjunction with cloned antigen-presenting cells and model membranes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI020248-08
Application #
3129799
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1983-08-01
Project End
1993-06-30
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Kincaid, Eleanor Z; Murata, Shigeo; Tanaka, Keiji et al. (2016) Specialized proteasome subunits have an essential role in the thymic selection of CD8(+) T cells. Nat Immunol 17:938-45
Rock, Kenneth L; Farfán-Arribas, Diego J; Colbert, Jeff D et al. (2014) Re-examining class-I presentation and the DRiP hypothesis. Trends Immunol 35:144-52
Colbert, Jeff D; Farfán-Arribas, Diego J; Rock, Kenneth L (2013) Substrate-induced protein stabilization reveals a predominant contribution from mature proteins to peptides presented on MHC class I. J Immunol 191:5410-9
Farfán-Arribas, Diego J; Stern, Lawrence J; Rock, Kenneth L (2012) Using intein catalysis to probe the origin of major histocompatibility complex class I-presented peptides. Proc Natl Acad Sci U S A 109:16998-7003
Meriin, Anatoli B; Mense, Martin; Colbert, Jeff D et al. (2012) A novel approach to recovery of function of mutant proteins by slowing down translation. J Biol Chem 287:34264-72
Kincaid, Eleanor Z; Che, Jenny W; York, Ian et al. (2012) Mice completely lacking immunoproteasomes show major changes in antigen presentation. Nat Immunol 13:129-35
Nguyen, Tina T; Chang, Shih-Chung; Evnouchidou, Irini et al. (2011) Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nat Struct Mol Biol 18:604-13
Georgiadou, Dimitra; Hearn, Arron; Evnouchidou, Irini et al. (2010) Placental leucine aminopeptidase efficiently generates mature antigenic peptides in vitro but in patterns distinct from endoplasmic reticulum aminopeptidase 1. J Immunol 185:1584-92
Hearn, Arron; York, Ian A; Bishop, Courtney et al. (2010) Characterizing the specificity and cooperation of aminopeptidases in the cytosol and endoplasmic reticulum during MHC class I antigen presentation. J Immunol 184:4725-32
Rock, Kenneth L; Farfan-Arribas, Diego J; Shen, Lianjun (2010) Proteases in MHC class I presentation and cross-presentation. J Immunol 184:9-15

Showing the most recent 10 out of 54 publications