PMID- 16220347 OWN - NLM STAT- MEDLINE DCOM- 20060120 LR - 20181113 IS - 0093-7711 (Print) IS - 0093-7711 (Linking) VI - 57 IP - 10 DP - 2005 Nov TI - Intrahaplotype and interhaplotype pairing of bovine leukocyte antigen DQA and DQB molecules generate functional DQ molecules important for priming CD4(+) T-lymphocyte responses. PG - 750-62 AB - 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. FAU - Norimine, Junzo AU - Norimine J AD - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. nori@vetmed.wsu.edu FAU - Brown, Wendy C AU - Brown WC LA - eng GR - R01-AI053692/AI/NIAID NIH HHS/United States GR - R01-AI30136/AI/NIAID NIH HHS/United States GR - R01-AI44005/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20051108 PL - United States TA - Immunogenetics JT - Immunogenetics JID - 0420404 RN - 0 (Antigens, Protozoan) RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (Bacterial Outer Membrane Proteins) RN - 0 (BoLA-DQA antigen) RN - 0 (BoLA-DQB antigen) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (p44 protein, Anaplasma phagocytophila) SB - IM MH - Amino Acid Sequence MH - Anaplasma marginale/immunology MH - Animals MH - *Antigen Presentation MH - Antigens, Protozoan/immunology MH - B7-1 Antigen/biosynthesis/immunology MH - B7-2 Antigen/biosynthesis/immunology MH - Babesia bovis/immunology MH - Bacterial Outer Membrane Proteins/immunology MH - CD4-Positive T-Lymphocytes/cytology/*immunology MH - Cattle MH - Cell Line MH - Cell Proliferation MH - *Haplotypes MH - Histocompatibility Antigens Class II/biosynthesis/genetics/*immunology MH - Humans MH - Molecular Sequence Data EDAT- 2005/10/13 09:00 MHDA- 2006/01/21 09:00 CRDT- 2005/10/13 09:00 PHST- 2005/05/26 00:00 [received] PHST- 2005/08/10 00:00 [accepted] PHST- 2005/10/13 09:00 [pubmed] PHST- 2006/01/21 09:00 [medline] PHST- 2005/10/13 09:00 [entrez] AID - 10.1007/s00251-005-0045-6 [doi] PST - ppublish SO - Immunogenetics. 2005 Nov;57(10):750-62. doi: 10.1007/s00251-005-0045-6. Epub 2005 Nov 8.