Antigen presentation by major histocompatibility complex (MHC) class I is a constitutive process in all nucleated cells. Antigens are peptides derived from both cellular and foreign proteins, and allow CD8+ T cells to distinguish self from non-self. For immune surveillance to be effective, cells must present a diverse repertoire of peptides derived from their intracellular environment to CD8+ T cells. This proposal describes an approach to characterize a non-canonical translation event, termed cryptic translation, which can direct the synthesis of peptides for MHCclass I presenting cells. One type of cryptic translation diverges sharply from conventional protein synthesis since a CUG start codon is decoded with leucine instead of the canonical AUG start codon with methionine. Using toeprinting and analytical centrifugation assays, these investigations will explain on a molecular level how ribosomes decode a CUG start codon using leucine. Cryptic peptides are envisaged to be a diverse subset of antigens that increase the complexity of targets for the immune system. A mechanistic understanding of this process will enable regulation of antigen presentation during immune surveillance and could promote the development of tumor vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI071468-03
Application #
7554118
Study Section
Special Emphasis Panel (ZRG1-F07-L (20))
Program Officer
Prograis, Lawrence J
Project Start
2006-01-01
Project End
2009-12-31
Budget Start
2009-01-01
Budget End
2009-12-31
Support Year
3
Fiscal Year
2009
Total Cost
$53,354
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704