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Functional specialization of HLA supertypes to different pathogen groups based on group-specific amino acid repertoire

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Akbik, R. (2019). Functional specialization of HLA supertypes to different pathogen groups based on group-specific amino acid repertoire. Master Thesis, Christian-Albrechts-Universität, Kiel.

Cite as: https://hdl.handle.net/21.11116/0000-0005-1EEA-3
HLA genes are essential immune genes coding for cell-surface proteins that are responsible in antigen presentation process regulating the immune response in humans. These genes are highly involved in host-parasite co-evolution. Previous research suggests that HLA-DRB1 alleles differ significantly in their ability to bind peptides from extracellular pathogens. The differential peptide recognition of DRB1 supertypes has been proposed to be linked to the distinct amino acid repertoires of these pathogens. Thus, this research firstly aims to explore the characteristic group-specific amino acid repertoires in pathogen. A significant difference was shown between the proteomes repertoire of different functional pathogen groups. However, Alanine amino acid has the highest contribution in the difference of amino acids repertoires between intracellular pathogen group and extracellular pathogen group. The second aim of the research was to analyze if there is binding-peptide specificity for these pathogen groups toward HLA-DRB1 supertypes. HLA alleles have potentially adapted their binding specificities to the different amino acid composition of groups of pathogen proteomes (intracellular and extracellular). A difference in binding peptides was revealed between the two functional pathogen groups across HLA-DRB1 alleles and supertypes: supertypes 9 and 3 showed a higher specificity toward intracellular pathogen peptides than extracellular ones. Answering these questions would serve in MHC evolution and immune research in general.