Medical Research

Stanford University

Joshua Elias
Stanford, CA
$1,000,000
June 2013

Our immune systems balance the vigilance required to kill cells compromised by infection or cancer with the tolerance needed to avoid harming healthy cells. The dynamic and complex repertoire of antigenic peptides nearly all cells present on major histocompatibility class I proteins (MHC 1) are the foundation of self-directed immune responses. Finding ways to sensitively and accurately measure these peptides (pMHC 1) is a long sought goal of immunologists. Past mass spectrometry-based efforts have been met with surprisingly low success rates, and were limited in their quantitative output. The team seeks to solve technical challenges that have hindered past efforts. By developing and applying a completely unbiased method for peptide analysis, they found that a surprisingly large proportion of pMHC 1 share essentially no homology with known proteins. While running counter to the established dogma, this finding opens new directions for the diagnosis and treatment of cancer. They will extend their methods in a quantitative fashion to exploit these non canonical peptides to better understand the antigenic contribution to B cell lymphomas. Specifically, the team will incorporate isotopic labeling into our peptide sequencing method, and use it to quantify how both canonical and non canonical pMHC 1 presentation changes with stress induction, and across increasingly neoplastic cell states.

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