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Related Experiment Videos

Polymorphism at the HLA-E locus predates most HLA-A and -B polymorphism.

D E Geraghty1, M Stockschleader, A Ishitani

  • 1Human Immunogenetics Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.

Human Immunology
|March 1, 1992
PubMed
Summary

The HLA-E locus shows low polymorphism with two identified alleles. These alleles are randomly associated with most HLA types, suggesting ancient origins and implications for bone marrow transplants.

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Area of Science:

  • Immunogenetics
  • Human Leukocyte Antigen (HLA) system

Background:

  • Classic human leukocyte antigen (HLA) class I antigens exhibit extensive polymorphism.
  • Nonclassic HLA antigens are characterized by low polymorphism.

Purpose of the Study:

  • To investigate the polymorphism of the HLA-E locus.
  • To define and characterize HLA-E alleles and their population frequencies.
  • To examine the association of HLA-E alleles with classical HLA antigens.

Main Methods:

  • DNA sequencing of cDNA from nine ethnically diverse individuals to identify polymorphisms.
  • Polymerase Chain Reaction (PCR) and oligonucleotide probe hybridization on genomic DNA from 90 HLA-typed individuals.
  • Analysis of allele frequencies and association with HLA-A and HLA-B haplotypes.

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Main Results:

  • No polymorphism was found in exons 1, 4-8, and the 3' untranslated exon of HLA-E.
  • Two base substitutions in exons 2 and 3 defined two HLA-E alleles, differing by an arginine to glycine change at position 107.
  • The two HLA-E alleles were found at nearly equal frequencies and showed random association with most HLA-A and HLA-B haplotypes, with a notable exception for the A1-B8 haplotype.

Conclusions:

  • The low polymorphism and random association of HLA-E alleles suggest they predate much of the HLA-A and -B polymorphism.
  • Natural selection appears to have maintained the HLA-E locus with minimal change.
  • A significant percentage of HLA-A and -B matched bone marrow donors may be mismatched at the HLA-E locus, impacting transplant outcomes.