HLA-DRB1 alleles control allergic bronchopulmonary aspergillosis-like pulmonary responses in humanized transgenic mice

J Allergy Clin Immunol. 2007 Sep;120(3):570-7. doi: 10.1016/j.jaci.2007.04.037. Epub 2007 Jun 11.


Background: Allergic bronchopulmonary aspergillosis (ABPA) is a lung hypersensitivity disease mediated in part by CD4(+) T(H)2 cells. There is a significant association between ABPA and the HLA-DR2 genotypes DRB1(*)1501 and DRB1(*)1503, whereas resistance might be associated with HLA-DRB1(*)1502.

Objective: We sought to elucidate the role of HLA-DR alleles in allergic inflammation in lungs.

Methods: HLA-DR humanized transgenic mice expressing either the susceptible or resistant alleles were analyzed for the nature and extent of pulmonary inflammation after exposure to Aspergillus species antigens.

Results: Exposed DRB1(*)1501 and DRB1(*)1503 transgenic mice displayed infiltrates made up prominently of eosinophils, which is consistent with the inflammation found in ABPA. The resistant DRB1(*)1502 mice, on the other hand, displayed minimal to moderate inflammation, consisting mainly of T-cell infiltrates. Significantly more mucin was produced in the DRB1(*)1503 and DRB1(*)1501 mice, and their ability to limit the number of Aspergillus species conidia within the lung parenchyma was impaired. Despite their differences, both the DRB1(*)1503 and DRB1(*)1502 strains mounted comparable T cell-proliferative responses to Aspergillus species antigens.

Conclusion: The HLA-DR2 alleles DRB1(*)1501 and DRB1(*)1503 play a major role in the development of allergic pulmonary inflammation. In contrast, the HLA-DR2 allele DRB1(*)1502 mediates a nonallergic T(H)1-like response to the organism, possibly explaining an ABPA resistance factor. These results are in support of our published human studies in patients with cystic fibrosis and asthma.

Clinical implications: HLA-DR typing in patients with cystic fibrosis and asthma will aid in the identification of individuals at risk for ABPA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • Aspergillosis, Allergic Bronchopulmonary / genetics*
  • Aspergillosis, Allergic Bronchopulmonary / immunology
  • Aspergillosis, Allergic Bronchopulmonary / pathology
  • Genetic Predisposition to Disease
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Humans
  • Immunoglobulin E / blood
  • Immunohistochemistry
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Lung / immunology*
  • Lung / pathology
  • Mice
  • Mice, Transgenic
  • Polymorphism, Genetic*


  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Immunoglobulin E