Immunology by numbers: quantitation of antigen presentation completes the quantitative milieu of systems immunology!

Anthony W Purcell1, Nathan P Croft1, David C Tscharke2

  • 1Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Insights

Mass spectrometry (MS) offers precise antigen presentation quantification by identifying MHC-bound peptides. This method surpasses biological readouts, enabling future large-scale immunopeptidome analysis.

Area of Science:

  • Immunology
  • Analytical Chemistry
  • Biochemistry

Background:

  • Antigen presentation is crucial for adaptive immunity.
  • Current methods for quantifying antigen presentation have limitations, including potential receptor cross-reactivity and variable dose responsiveness.
  • There is a need for more precise and definitive methods to study antigen presentation.

Purpose of the Study:

  • To review current approaches for quantifying antigen presentation.
  • To highlight the role of mass spectrometry (MS) in defining and quantifying MHC-bound peptides.
  • To discuss the future potential of MS and big data in immunopeptidomics.

Main Methods:

  • Review of existing biological and biochemical readouts for antigen presentation.
  • Focus on mass spectrometry (MS) techniques, including high mass accuracy and tandem MS (MS/MS) for peptide identification.
  • Discussion of big data approaches for analyzing immunopeptidomes.

Main Results:

  • Mass spectrometry provides unambiguous identification of MHC-bound peptides through accurate mass determination and fragmentation patterns.
  • MS overcomes limitations of biological readouts, such as cross-reactivity and variable dose responses.
  • The study anticipates the future quantification of whole immunopeptidomes using big data MS approaches.

Conclusions:

  • Mass spectrometry is a powerful and definitive tool for quantifying antigen presentation at the cell surface.
  • MS offers superior specificity and accuracy compared to traditional biological assays.
  • Future applications of MS in big data analysis will advance the field of immunopeptidomics for both in vitro and in vivo studies.

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