Determinants of Epitope Immunodominance Hierarchies in Protein Antigens at the Molecular, Structural, and Cellular...

Epitope immunodominance describes the phenomenon whereby some antigenic epitopes preferentially elicit immune responses, whereas other epitopes remain subdominant or immunologically silent. Epitope immunodominance hierarchies are the result of coordinated molecular, structural, and cellular mechanisms. These hierarchies emerge from selective immune recognition processes that balance effective immunity and self-tolerance mechanisms.

The aim of this study is to describe the molecular, structural, and cellular parameters that mediate epitope immunodominance in antigens. In addition, it details how central and peripheral tolerance mechanisms influence epitope selection and immunodominance hierarchies in T- and B-cell responses.

Epitope immunodominance arises from molecular and structural characteristics, including the nature of the antigen, the level of protein structure, host genetic factors, and immune regulatory mechanisms. Epitope immunodominance hierarchies depend on multiple factors, including the structural accessibility of epitopes, the epitope density, the distinctive binding affinities of antigen-derived peptides to MHC molecules, the availability of T cells able to recognize peptide-MHC complexes, the molecular stability of conformational epitopes recognized by BCRs, and the efficiency of antigen processing by antigen-presenting cells. Collectively, these factors focus immune recognition, determining whether specific epitopes dominate the immune response or remain immunologically silent.