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Related Experiment Video

Updated: Feb 4, 2026

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
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Evolutionary Pressure against MHC Class II Binding Cancer Mutations.

Rachel Marty Pyke1, Wesley Kurt Thompson2, Rany M Salem3

  • 1Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093, USA.

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|September 25, 2018
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CD4+ T cells play a crucial role in anti-tumor immunity by influencing tumor evolution. MHC-II presentation constrains cancer mutations, impacting tumor development and highlighting the importance of CD4+ T cell responses.

Keywords:
MHC-IIT cellscancerdriver mutationsimmune editingimmunityimmunotherapytumor evolution

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Area of Science:

  • Immunology
  • Cancer Biology
  • Genomics

Background:

  • Anti-cancer immunity relies on CD8+ T cells recognizing neoantigens via MHC-I.
  • The role of CD4+ T cells and MHC-II presentation in neoantigen selection and tumor evolution remains understudied.

Purpose of the Study:

  • To investigate how MHC-II genotype influences the mutational landscape during tumorigenesis.
  • To compare the impact of MHC-I and MHC-II presentation on tumor evolution.

Main Methods:

  • Computational modeling of MHC-II presentation for 1,018 driver mutations across 5,942 tumors.
  • Analysis of mutation selection pressures related to MHC-I and MHC-II binding.

Main Results:

  • MHC-II genotype significantly constrains tumor mutations, complementing MHC-I.
  • Mutations poorly presented by MHC-II are positively selected during tumorigenesis, exceeding MHC-I effects.
  • Less inter-patient variation in MHC-II presentation compared to MHC-I was observed.
  • Age at diagnosis correlated with MHC-I presentation but not MHC-II.

Conclusions:

  • MHC-II presentation plays a central role in shaping tumor evolution.
  • CD4+ T cell responses are critical drivers of anti-tumor immunity and tumor development.
  • Understanding MHC-II's influence provides complementary insights to MHC-I in cancer immunology.