Characterization of equine major histocompatibility complex (MHC) haplotype diversity and pathogen correlations

Background and RationaleThe major histocompatibility complex (MHC) gene products play an important role in innate and adaptive immune responses and may affect the development of autoimmune diseases and susceptibility or resistance to pathogens. It is known that MHC genes are the most polymorphic genes within the vertebrate genome. In wild species, high polymorphism is maintained by balancing selection: (i) MHC heterozygotes are believed to be preferred over MHC homozygotes because they can present a wider range of antigens. (ii) Specific MHC alleles are favored that ensure protection against pathogens currently present in the environment. In the latter case, the preference for MHC changes over time together with the change in pathogen composition. In contrast, domestic animals undergo artificial selection. Thus, in addition to pathogen/fitness-related pressure, the pool of MHC genes present in domestic animals may be influenced by a human preference for specific traits. Hence, artificial selection, as performed in the case of domestic animals, may influence MHC diversity (reviewed in Hammer et al. 2020).MHC haplotypes can play an important role in determining an individual’s susceptibility or resistance to various pathogens. In people with hepatitis C virus (HCV) infection, an association between certain human leukocyte antigens (HLA) with virus persistence or clearance was found (Ali et al. 2010). Similarly, in equine herpes virus type 1 (EHV-1) infection MHC-restricted responses of cytotoxic T lymphocytes (CTL) against viral protein were shown (Kydd et al. 2014, Sohrmann et al. 2019). Common equine pathogens like EHV-1 or Streptococcus equi ssp. equi frequently lead to outbreaks of infections resulting in significant economic losses. Thus, improving our knowledge on the genetic aspects and immunity against these pathogens is of great interest to equine health. A more recently detected equine pathogen, the equine hepacivirus (EqHV), shares similarities with HCV (Pfaender et al. 2017, Badenhorst et al. 2022). Since MHC haplotypes are important in determining the course of HCV infection, this association might also be of importance in equine hepacivirus infections.Project AimsThe study aims to investigate the polymorphism of MHC within and between three breeds of horses, Lipizzaner, Shetland ponies, and Warmblood horses. We want to assess the MHC diversity by determining the polymorphism of MHC microsatellites and MHC haplotypes. Use of the same MHC microsatellites will allow comparison of the results with those for previously tested horse populations. More importantly, we analyze the associations and correlations between particular MHC haplotypes with the immune response against certain equine pathogens of interest.Main Hypotheses• The bacterial or viral loads in infected horses correlate with certain MHC haplotypes.• Infected horses show a higher frequency of activated lymphocytes and/ or higher serum cytokine levels.• The CD4/CD8 T cell responses to the pathogens of interest can be attributed to certain equine MHC haplotypes.

Klinisches Zentrum für Pferde
Zentrum für Pathobiologie
Klinisches Zentrum für Pferde