The MHC I immunopeptidome conveys to the cell surface an integrative view of cellular regulation

Mol Syst Biol. 2011 Sep 27;7:533. doi: 10.1038/msb.2011.68.

Abstract

Self/non-self discrimination is a fundamental requirement of life. Endogenous peptides presented by major histocompatibility complex class I (MHC I) molecules represent the essence of self for CD8 T lymphocytes. These MHC I peptides (MIPs) are collectively referred to as the immunopeptidome. From a systems-level perspective, very little is known about the origin, composition and plasticity of the immunopeptidome. Here, we show that the immunopeptidome, and therefore the nature of the immune self, is plastic and moulded by cellular metabolic activity. By using a quantitative high-throughput mass spectrometry-based approach, we found that altering cellular metabolism via the inhibition of the mammalian target of rapamycin results in dynamic changes in the cell surface MIPs landscape. Moreover, we provide systems-level evidence that the immunopeptidome projects at the cell surface a representation of biochemical networks and metabolic events regulated at multiple levels inside the cell. Our findings open up new perspectives in systems immunology and predictive biology. Indeed, predicting variations in the immunopeptidome in response to cell-intrinsic and -extrinsic factors could be relevant to the rational design of immunotherapeutic interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • Cell Membrane / genetics
  • Cell Membrane / immunology
  • Gene Expression Profiling
  • High-Throughput Screening Assays
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Immunity*
  • Major Histocompatibility Complex / genetics*
  • Major Histocompatibility Complex / immunology
  • Mass Spectrometry
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / genetics*
  • Metabolic Networks and Pathways / immunology
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Peptides / genetics
  • Peptides / immunology
  • Proteomics*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Signal Transduction / immunology
  • Sirolimus / pharmacology*
  • Systems Biology / methods
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / immunology
  • TOR Serine-Threonine Kinases / metabolism*
  • Tandem Mass Spectrometry

Substances

  • Histocompatibility Antigens Class I
  • Peptides
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Sirolimus