The major histocompatibility complex (MHC) and Killer Inhibitory Receptor (KIR) genetic loci are shown to have strong influences on the outcomes of infectious diseases, cancers, inflammatory/autoimmune diseases, reproduction, and transplantation. Recent advances in characterizing human leukocyte antigen (HLA) and KIR diversity in human populations have led to translational impacts for bone marrow and solid organ transplant matching. In the past decade, prediction-based matching has become standard for bone marrow registries which has led to improvements in match rates and transplant outcomes. Genotyping of the KIR system has started moving into standard use clinically and as a screening test for potential donors. Solid organ allocation algorithms are incorporating more population genetics methods to help improve equity and outcomes.
There is currently robust discussion on the origins of HLA and KIR polymorphisms, but limited information on the effects of the polymorphisms on interactions mediated by HLA and KIR. While both the HLA and KIR regions have been associated with diseases and their outcomes, the interactions between those regions have had limited attention.
This Research Topic aims to discuss recent advances in HLA and KIR population genetics and dynamics, and their impacts on cellular therapies such as transplantation. Additionally, we will discuss novel functional aspects of the HLA and KIR polymorphisms, biology and disease associations.
We welcome the submission of Original Research and Review articles covering the following areas:
• MHC/HLA expression variations, antigen presentation pathways and function in autoimmunity, viral diseases, and transplantation.
• Maternal KIR and fetal HLA-C as determinants of reproductive success/failure in first and subsequent pregnancies.
• MHC background and the NK cell inhibitory receptor repertoires – what is the connection?
• Human and macaque KIR haplotypes – evolution, selection and roles in transplantation and reproduction.
• Should the purpose of HLA registries be changed to address preventative precision medicine? How large should the registries be? What new information should be included in their entries (for example, non-classical HLAs, KIRs, MHC expression levels)? How can we create a pilot for such a registry? What are the ethical issues associated with such registries?
• Computational issues related to HLA/KIR databases, data mining, and faster donor matching.
• Population admixture severely complicates finding donors: How can this be addressed? Can we target donor recruitment to cover population diversity in an age of unprecedented admixture?
• Mathematical modeling of NK cell responses to pathogens, in order to gain new insights into viral evasion mechanisms and host-viral evolution, as well as the co-evolution of the KIR and HLA loci.
The major histocompatibility complex (MHC) and Killer Inhibitory Receptor (KIR) genetic loci are shown to have strong influences on the outcomes of infectious diseases, cancers, inflammatory/autoimmune diseases, reproduction, and transplantation. Recent advances in characterizing human leukocyte antigen (HLA) and KIR diversity in human populations have led to translational impacts for bone marrow and solid organ transplant matching. In the past decade, prediction-based matching has become standard for bone marrow registries which has led to improvements in match rates and transplant outcomes. Genotyping of the KIR system has started moving into standard use clinically and as a screening test for potential donors. Solid organ allocation algorithms are incorporating more population genetics methods to help improve equity and outcomes.
There is currently robust discussion on the origins of HLA and KIR polymorphisms, but limited information on the effects of the polymorphisms on interactions mediated by HLA and KIR. While both the HLA and KIR regions have been associated with diseases and their outcomes, the interactions between those regions have had limited attention.
This Research Topic aims to discuss recent advances in HLA and KIR population genetics and dynamics, and their impacts on cellular therapies such as transplantation. Additionally, we will discuss novel functional aspects of the HLA and KIR polymorphisms, biology and disease associations.
We welcome the submission of Original Research and Review articles covering the following areas:
• MHC/HLA expression variations, antigen presentation pathways and function in autoimmunity, viral diseases, and transplantation.
• Maternal KIR and fetal HLA-C as determinants of reproductive success/failure in first and subsequent pregnancies.
• MHC background and the NK cell inhibitory receptor repertoires – what is the connection?
• Human and macaque KIR haplotypes – evolution, selection and roles in transplantation and reproduction.
• Should the purpose of HLA registries be changed to address preventative precision medicine? How large should the registries be? What new information should be included in their entries (for example, non-classical HLAs, KIRs, MHC expression levels)? How can we create a pilot for such a registry? What are the ethical issues associated with such registries?
• Computational issues related to HLA/KIR databases, data mining, and faster donor matching.
• Population admixture severely complicates finding donors: How can this be addressed? Can we target donor recruitment to cover population diversity in an age of unprecedented admixture?
• Mathematical modeling of NK cell responses to pathogens, in order to gain new insights into viral evasion mechanisms and host-viral evolution, as well as the co-evolution of the KIR and HLA loci.