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Immunogenetics

, Volume 57, Issue 10, pp 750–762 | Cite as

Intrahaplotype and interhaplotype pairing of bovine leukocyte antigen DQA and DQB molecules generate functional DQ molecules important for priming CD4+ T-lymphocyte responses

  • Junzo Norimine
  • Wendy C. Brown
Original Paper

Abstract

Antigen-specific CD4+ T-lymphocyte responses are restricted by major histocompatibility complex class II molecules, which influence T-cell priming during infection. Human leukocyte antigen (HLA) and bovine leukocyte antigen (BoLA) DRB3 and DQ genes are polymorphic, but unlike HLA, many BoLA haplotypes have duplicated DQ genes, and antibody-blocking studies indicated that BoLA-DQ molecules present various pathogen epitopes. Limited experimentation also suggested that BoLA-DQ molecules formed by interhaplotype pairing of A and B chains are functional. To compare antigen presentation by DR and DQ molecules and to definitively demonstrate functional BoLA-DQ molecules derived from interhaplotype pairing, different combinations of DR or DQ A and B proteins were expressed with CD80 in 293-F cells for use as antigen-presenting cells (APCs). This approach identified 11 unique restriction elements including five DR and six DQ pairs for antigen-specific CD4+ T-cell responses against tick-transmitted bovine hemoparasites Anaplasma marginale or Babesia bovis. Interhaplotype pairing of DQ A and B molecules was demonstrated. Testing of six expressed DQA/B pairs from an animal with duplicated DQ haplotypes (DH16A/DH22H) demonstrated that an interhaplotype pair, DQA*2206/DQB*1301, presented A. marginale peptide B. In DH22H and DH16A homozygous animals, DQA*2206 was tightly linked with DQB*1402, and DQA*22021 was linked with DQB*1301. APCs from these donors could not present peptide B, confirming that DQA*2206/DQB*1301 encoded a functional interhaplotype pair. Functional BoLA-DQ molecules are generated by both intrahaplotype and interhaplotype pairing of A and B chains and play a similar role to BoLA-DR in priming helper T-cell responses to important pathogens.

Keywords

BoLA-MHC class II DQA DQB Cattle Interhaplotype pairing 

Notes

Acknowledgements

We thank Kimberly Kegerreis, Shelley Whidbee, and Emma Karel for excellent technical assistance, Dr. Christopher J. Davies for information of BoLA-DQ expression in cattle with homozygous haplotypes and for helpful comments on the manuscript, and Dr. John Swain for providing blood samples from calves at the WSU Dairy. This work was supported by grants R01-AI30136, R01-AI44005, and R01-AI053692 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) and by the US Department of Agriculture (USDA) Cooperative Agreement 58-5348-044. These experiments are in compliance with USDA and NIH guidelines for vertebrate animal use.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Veterinary Microbiology and PathologyWashington State UniversityPullmanUSA

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