Evolutionary Pressure against MHC Class II Binding Cancer Mutations.

ABSTRACT: The anti-cancer immune response against mutated peptides of potential immunological relevance (neoantigens) is primarily attributed to MHC-I-restricted cytotoxic CD8⁺ T cell responses. MHC-II-restricted CD4⁺ T cells also drive anti-tumor responses, but their relation to neoantigen selection and tumor evolution has not been systematically studied. Modeling the potential of an individual's MHC-II genotype to present 1,018 driver mutations in 5,942 tumors, we demonstrate that the MHC-II genotype constrains the mutational landscape during tumorigenesis in a manner complementary to MHC-I. Mutations poorly bound to MHC-II are positively selected during tumorigenesis, even more than mutations poorly bound to MHC-I. This emphasizes the importance of CD4⁺ T cells in

SUBMITTER: Marty Pyke R 

PROVIDER: S-EPMC6482006 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature