Unconventional Sources of Peptides for Antigen Presentation

NIH Pandemic-Era Grants

Pandemic Era Grants

2020

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Principal Investigator: Scheherazade  Sadegh-Nasseri
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2020
Award: $543,021
Funding agency: National Institute of Allergy and Infectious Diseases

Unconventional sources of peptides for antigen presentation
Project Abstract
 The long term goals of this project are to understand how the antigen processing pathway generates
peptide/MHC class I complexes (pMHC I) by cryptic translation. Numerous studies, from different
laboratories, have shown that naturally processed pMHC I on the surface of tumors, virally infected cells,
transfected or even normal cells arise from regions of mRNAs that were not expected to be translated.
The mechanism that allows cells to sample this cryptic source of antigenic precursors versus other
conventional sources are poorly understood. Moreover, the conditions that enhance presentation of cryptic
peptides in cells are not well defined.
 Here we will test the hypotheses that (a) cryptic pMHC arise due to translation initiated by a distinct
and novel set of tRNAs and ribosomes, (b) expression of cryptic pMHC I is regulated in cells under stress,
and (c) the eIF2A translation initiation factor makes a key contribution to the cryptic pMHC I repertoire and
immunity.
 We anticipate that an improved understanding of how cryptic pMHC I are generated will not only
provide a means to tap into a novel sources of antigenic peptides and new approaches to vaccine design
for intractable viruses and cancer, but will also yield new insights into protein translation and immune
surveillance mechanisms.
 

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