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Published on: February 6, 2018
THE SPECIFICITY OF ANTI-HLA CLASS II MONOCLONAL ANTIBODIES IN CATTLE
Ph R Nilsson1, S G E Marsh1, I Joosten1
1Department of Animal Husbandry and ,Department of Experimental Animal Morphology and Cell Biology, Agricultural University, Wageningen, the Netherlands; ,Anthony Nolan Research Institute, Royal Free Hospital, London, UK; ,Transplantation Serology Laboratory, University Hospital Nijmegen, Nijmegen, the Netherlands; ,Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University of Utrecht, Utrecht, the Netherlands; ,Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden; ,Department of Molecular Biology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; and ,Department of Immunohaematology and Bloodbank, University Hospital, Leiden, the Netherlands.
Human leukocyte antigen (HLA) class II monoclonal antibodies (mAb) showed cross-reactivity with bovine lymphocytes. This suggests that HLA antibody reactivity patterns are not solely determined by single epitopes.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Numerous anti-human leukocyte antigen (HLA) class II monoclonal antibodies (mAb) were tested at the Eleventh International HLA Histocompatibility Workshop.
- Epitopes for binding were mapped within the antigen-binding site of class II molecules for polymorphic mAb.
- Key amino acid (AA) motifs of these epitopes were found in bovine DRB3 and DQB sequences, raising questions about interspecies cross-reactivity.
Purpose of the Study:
- To investigate the potential interspecies cross-reactivity of anti-HLA class II mAb with bovine lymphocytes.
- To determine if shared AA motifs between human and bovine HLA molecules lead to cross-reactivity.
- To analyze the reactivity patterns of specific anti-HLA class II mAb against bovine lymphocytes.
Main Methods:
- Selection of eight polymorphic anti-HLA class II mAb (seven anti-HLA DRB1, one anti-HLA DQB) and one monomorphic anti-HLA class II mAb (7.5.10.1).
- Testing mAb reactivity towards bovine lymphocytes using flow cytometry and lymphocyte microcytotoxicity assays.
- Biochemical analysis to support flow cytometry and microcytotoxicity findings.
Main Results:
- Five of the polymorphic anti-HLA class II mAb exhibited reactivity with bovine lymphocytes.
- The anti-bovine reactivity of the monomorphic mAb 7.5.10.1 was confirmed.
- Biochemical analysis supported the observed cross-reactivity, but the anti-bovine reactions did not always align with expected recognition based on postulated AA motifs.
Conclusions:
- Some anti-HLA class II mAb demonstrate cross-reactivity with bovine lymphocytes.
- The presence of shared AA motifs does not always predict interspecies cross-reactivity.
- HLA antibody reactivity patterns may not be solely determined by single epitopes, suggesting complex interactions or multiple epitope recognition.
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