Abstract
During the display of peptide/human leukocyte antigen (HLA) -I complex for further immune recognition, the cleaved and transported antigenic peptides have to bind to HLA-I protein and the binding affinity between peptide epitopes and HLA proteins directly influences the immune recognition ability in human beings. Key factors affecting the binding affinity during the generation, selection and presentation processes of HLA-I complex have not yet been fully discovered. In this study, a new method describing the HLA class I-peptide interactions was proposed. Three hundred and forty features of HLA I proteins and peptide sequences were utilized for analysis by four candidate algorithms, screening the optimal classifier. Features derived from the optimal classifier were further selected and systematically analyzed, revealing the core regulators. The results validated the hypothesis that features of HLA I proteins and related peptides simultaneously affect the binding process, though with discrepant redundancy. Besides, the high relative ratio (16/20) of the amino acid composition features suggests the unique role of sequence signatures for the binding processes. Integrating biological, evolutionary and chemical features of both HLA I molecules and peptides, this study may provide a new perspective of the underlying mechanisms of HLA I-mediated immune reactions.
Highlights
Human leukocyte antigen (HLA), which refers in particular to the major histocompatibility complex (MHC) in humans, is a group of cell surface proteins that is essential for the recognition of self-cells and non-self-cells and activation of the acquired immune system to eliminate the non-self-components[1,2]
Various influential factors have been revealed to contribute to the specific peptide generation, binding selection and presentation processes of HLA-I/peptide complexes and related immune reactions against endogenous antigens, the principle factors determining the peptide binding specificity to different HLA I molecules during various biological stages have not been fully discovered
The 340-dimensional features are ranked according to the two criteria: the features that are evaluated by maximal relevance are listed in the MaxRel feature list, and the features that are ordered by the maximal relevance and minimal redundancy are listed in the mRMR feature list
Summary
Human leukocyte antigen (HLA), which refers in particular to the major histocompatibility complex (MHC) in humans, is a group of cell surface proteins that is essential for the recognition of self-cells and non-self-cells and activation of the acquired immune system to eliminate the non-self-components[1,2]. Various influential factors have been revealed to contribute to the specific peptide generation, binding selection and presentation processes of HLA-I/peptide complexes and related immune reactions against endogenous antigens, the principle factors determining the peptide binding specificity to different HLA I molecules during various biological stages have not been fully discovered. We proposed a new computational method to discover the core regulators for HLA-I/peptide binding affinity during the integrated peptide generation, binding selection and presentation processes based on the Immune Epitope Database (IEDB)[19] This data set has been validated to integrate various immune-associated databases, including more than 95% of the manually curated, relevant published literature, aggregating more than 15,000 journal articles and more than 704,000 experiments. This study may provide a new perspective for developing studies of HLA I-mediated immune reactions
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