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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
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Natural Selection on HLA-DPB1 Amino Acids Operates Primarily on DP Serologic Categories.

Richard M Single1, Steven J Mack2, Owen D Solberg3

  • 1Department of Mathematics and Statistics, University of Vermont, Burlington, VT, United States.

Human Immunology
|October 26, 2024
PubMed
Summary

Balancing selection maintains diversity in Human Leukocyte Antigen (HLA) DP serologic categories (SCs), not DPB1 alleles or T-cell epitopes. This selection shapes the global distribution of DP SCs across different world regions.

Keywords:
Amino acidBalancing selectionDP serologic categoriesDPB1Population study

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Area of Science:

  • Immunogenetics
  • Population Genetics
  • Molecular Evolution

Background:

  • The Human Leukocyte Antigen (HLA) DPB1 locus shows allele frequencies influenced by genetic drift.
  • Specific DPβ amino acid frequencies suggest balancing selection acting on this HLA locus.
  • Understanding selection pressures on HLA diversity is crucial for immunology and transplantation.

Purpose of the Study:

  • To investigate the influence of natural selection on DPB1 diversity.
  • To analyze three functional categories: DPB1 T-cell epitopes, supertypes, and serologic categories (SCs).
  • To examine the global distribution and evolutionary forces shaping DP SCs.

Main Methods:

  • Ewens-Watterson (EW) selective neutrality analysis was applied to worldwide population data.
  • Asymmetric Linkage Disequilibrium (ALD) analysis was used to study haplotype associations.
  • 136 worldwide populations were analyzed for DPB1 diversity and DPA1 allele associations.

Main Results:

  • EW analyses provided strong evidence for balancing selection on DP serologic categories (SCs).
  • No evidence of balancing selection was found for DPB1 T-cell epitopes or supertypes.
  • Distinct DP SCs exhibit regional global distributions, with DP2 SC being universally present.

Conclusions:

  • Natural selection primarily maintains population-level diversity of DP SCs.
  • Balancing selection does not appear to be the main driver for DPB1 alleles or T-cell epitopes.
  • Haplotype associations between DPA1 and DP SCs are influenced by specific DPβ amino acid variations.