Role of human and porcine MHC DRB1 alleles in determining the intensity of individual human anti-pig T-cell responses.
Alleles
Amino Acid Sequence
Animals
Antigens, Heterophile
/ immunology
Biological Variation, Individual
Genotype
HLA-DRB1 Chains
/ genetics
Haplotypes
Histocompatibility Antigens Class II
/ immunology
Humans
Interferon-gamma
/ biosynthesis
Killer Cells, Natural
/ metabolism
Leukocytes, Mononuclear
/ immunology
Lymphocyte Activation
Rats
Sequence Alignment
Sequence Homology, Amino Acid
Swine
/ immunology
T-Cell Antigen Receptor Specificity
/ immunology
T-Lymphocytes
/ immunology
HLA-SLA matching
MHC typing
Journal
Xenotransplantation
ISSN: 1399-3089
Titre abrégé: Xenotransplantation
Pays: Denmark
ID NLM: 9438793
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
12
11
2018
revised:
10
04
2019
accepted:
12
04
2019
pubmed:
11
5
2019
medline:
14
4
2020
entrez:
11
5
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Substances chimiques
Antigens, Heterophile
0
HLA-DRB1 Chains
0
Histocompatibility Antigens Class II
0
IFNG protein, human
0
SLA-DRB1 antigen
0
Interferon-gamma
82115-62-6
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12523Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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