Role of human and porcine MHC DRB1 alleles in determining the intensity of individual human anti‐pig T‐cell responses
Background Differences in quality and strength of immune responses between individuals are mainly due to polymorphisms in major histocompatibility complex (MHC) molecules. Focusing on MHC class‐II, we asked whether the intensity of human anti‐pig T‐cell responses is influenced by genetic variability in the human HLA‐DRB1 and/or the porcine SLA‐DRB1 locus. Methods ELISpot assays were performed using peripheral blood mononuclear cells (PBMCs) from 62 HLA‐DRB1‐typed blood donors as responder and the porcine B cell line L23 as stimulator cells. Based on the frequency of IFN‐γ‐secreting cells, groups of weak, medium, and strong responder individuals were defined. Mixed lymphocyte reaction (MLR) assays were performed to study the stimulatory capacity of porcine PBMCs expressing different SLA‐DRB1 alleles. Results Concerning the MHC class‐II configuration of human cells, we found a significant overrepresentation of HLA‐DRB1*01 alleles in the medium/strong responder group as compared to individuals showing weak responses to stimulation with L23 cells. Evaluation of the role of MHC class‐II variability in porcine stimulators revealed that cells expressing SLA‐DRB1*06 alleles triggered strong proliferation in approximately 70% of humans. Comparison of amino acid sequences indicated that strong human anti‐pig reactivity may be associated with a high rate of similarity between human and pig HLA/SLA‐DRB1 alleles. Conclusion Variability in human and porcine MHC determines the intensity of individual human anti‐pig T‐cell responses. MHC typing and cross‐matching of prospective recipients of xenografts and donor pigs could be relevant to select for donor‐recipient combinations with minimal anti‐porcine immunity.
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