<p>The theory of immunosurveillance posits that T cells eliminate clones harboring nonself-antigens generated by somatic mutations. Although a role of immunosurveillance in cancer is supported by evidence, whether it affects precancerous expansions has not been well established. Here we studied the association between MHC–variant binding and risk of clonal hematopoiesis (CH), a blood precancer state, predicting MHC binding affinity toward CH hotspot variants in 380,000 UK Biobank participants and examining the relationship between predicted binding to each variant and its expansion risk. Despite the study being powered to detect subtle differences in selective pressure, we did not find associations between predicted binding and CH prevalence for any of the examined variants. In CH-affected individuals, we identified no relationship between predicted variant binding and clone size. Overall, we found no evidence that the MHC genotype affects which variants expand in CH, suggesting a limited role for immunosurveillance in shaping clonal expansions in the blood.</p>

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No evidence of immunosurveillance in mutation-hotspot-driven clonal hematopoiesis

  • Barbara Walkowiak,
  • Hamish A. J. MacGregor,
  • Jamie R. Blundell

摘要

The theory of immunosurveillance posits that T cells eliminate clones harboring nonself-antigens generated by somatic mutations. Although a role of immunosurveillance in cancer is supported by evidence, whether it affects precancerous expansions has not been well established. Here we studied the association between MHC–variant binding and risk of clonal hematopoiesis (CH), a blood precancer state, predicting MHC binding affinity toward CH hotspot variants in 380,000 UK Biobank participants and examining the relationship between predicted binding to each variant and its expansion risk. Despite the study being powered to detect subtle differences in selective pressure, we did not find associations between predicted binding and CH prevalence for any of the examined variants. In CH-affected individuals, we identified no relationship between predicted variant binding and clone size. Overall, we found no evidence that the MHC genotype affects which variants expand in CH, suggesting a limited role for immunosurveillance in shaping clonal expansions in the blood.