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The "minimal essential MHC" revisited: both peptide-binding and cell surface expression level of MHC molecules are
1Institute for Animal Health, Compton, Berkshire, U.K.
Abstract:
Birds, like mammals, have a highly polymorphic MHC that determines strong allograft rejection. However, in contrast to mammals, there are a number of viral diseases for which resistance and susceptibility are determined by particular chicken MHC haplotypes. We have found that certain common chicken MHC haplotypes express only one class I molecule at high levels. The selection on a single MHC gene should be strong, in contrast to the situation in mammals. We have determined the peptide motifs for the dominant class I molecules from a number of chicken MHC haplotypes and found that they can explain the outcome of infections with a small virus. However, the strongest MHC association is the resistance of the chicken B21 haplotype to classical Marek's disease virus, a relatively large pathogen for which any MHC molecule should find peptides. In 40 chicken lines, the level of class I expression correlates with the level of MHC-determined susceptibility to Marek's disease, the most susceptible B19 with the highest expression and the most resistant B21 with the lowest expression. Thus, cell surface expression level of class I molecules appears to be a polymorphism under selection by infectious pathogens, just like peptide-binding specificity. We speculate that these expression level differences are another manifestation of the simple MHC of chickens, which in human and mouse haplotypes are averaged out.
Insights
Chicken MHC class I expression levels, not just peptide binding, influence disease resistance. Lower expression in the B21 haplotype correlates with Marek's disease virus resistance, unlike other haplotypes.
Area of Science:
- Immunogenetics
- Avian Virology
- Molecular Biology
Background:
- Birds possess a polymorphic Major Histocompatibility Complex (MHC), similar to mammals, influencing allograft rejection.
- Unlike mammals, specific chicken MHC haplotypes are linked to resistance or susceptibility to certain viral diseases.
Purpose of the Study:
- To investigate the role of chicken MHC class I molecules in disease resistance.
- To determine if peptide-binding specificity or expression levels of MHC class I molecules are key factors in pathogen resistance.
Main Methods:
- Determined peptide-binding motifs for dominant class I molecules from various chicken MHC haplotypes.
- Correlated MHC class I expression levels with susceptibility/resistance to Marek's disease virus across 40 chicken lines.
Main Results:
- Peptide-binding motifs of MHC class I molecules explained outcomes for small virus infections.
- Chicken MHC class I expression levels correlated with Marek's disease virus susceptibility; B19 (susceptible) showed highest expression, B21 (resistant) showed lowest.
- The B21 haplotype exhibited strong resistance to Marek's disease virus.
Conclusions:
- Both peptide-binding specificity and cell surface expression levels of MHC class I molecules are under selection by infectious pathogens in chickens.
- Expression level polymorphism of MHC class I molecules may be a unique feature of the simpler chicken MHC system compared to mammals.