Analysis of the degradation mechanisms of MHC class I-presented tumor antigenic peptides by high performance liquid chromatography/electrospray ionization mass spectrometry: application to the design of peptidase-resistant analogs
✍ Scribed by Maha Ayyoub; Bernard Monsarrat; Honoré Mazarguil; Jean Edouard Gairin
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 411 KB
- Volume
- 12
- Category
- Article
- ISSN
- 0951-4198
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✦ Synopsis
Peptide vaccines based on the use of MHC class I restricted epitopes are currently assayed for anti-tumor and anti-viral immunotherapy. With the aim of designing minimally modified, peptidase-resistant analogs, we developed a rational approach based on a detailed understanding of the degradation mechanism of peptides in serum. Degradation of murine tumor antigen P198 and human tumor antigen MAGE-3.A1 was followed by on line high performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS). This method provided high precision and sensitivity for rapid and direct analysis of degradation fragments in a complex mixture and, very importantly, precise identification of transient degradation fragments present at low concentrations. The design of structurally modified analogs, and the analysis of their degradation by on-line HPLC/ESI-MS, allowed us to demonstrate the efficiency of local modifications in the protection of a given peptide bond towards a specific peptidase activity.