Systems and methods for identifying hla-associated tumor peptides

A method of determining amino acid sequences of peptides that bind to an MHC-I or HLA-I complex or an MHC-II or HLA-II complex, comprising:

• obtaining a sample comprising unlabeled isolated peptides from an MHC-I or HLA-I complex or an MHC-II or HLA-II complex;
• adding one or more labeled peptides to the sample to form a mixed sample comprising the labeled peptides and the unlabeled isolated peptides;
• analyzing the mixed sample with an LC-MS/MS system to produce survey mass spectrometry scans of the sample;
• integrating into the LC-MS/MS system a target label filter based on the survey mass spectrometry scans to monitor a list of the one or more labeled peptides, thereby creating an integrated LC-MS/MS system;
• analyzing the mixed sample continuously with the integrated LC-MS/MS system, wherein detection of the one or more labeled peptides triggers the LC-MS/MS system to scan unlabeled isolated peptides until the integrated LC-MS/MS no longer detects the one or more labeled peptides;
• wherein the integrated LC-MS/MS system alternates between obtaining survey scans and scans of the one or more labeled peptides for the detection of endogenous peptides having the identical amino acid sequence of the one or more labeled peptides, respectively, and determining the amino acid sequence of the unlabeled isolated peptides scanned by integrated LC-MS/MS system.