Determining positional bias of MHC class I restricted T-cell epitopes in viral antigens
After viral infection, CD8+ T-cells can rapidly detect their intracellular presence by recognizing peptide fragments presented by MHC class I molecules on the cell surface that are derived from degraded viral protein. This appears to be in conflict with the observation that viral proteins have relatively long half-lives. To explain this, the DRiPs hypothesis (Yewdell and Nicchitta, 2006) was proposed, which states that these epitopes come from Defective Ribosomal Products (DRiPs), rather than degradation of mature protein products. If epitopes do come from defective ribosomal products, this could lead to a positional bias of epitopes in their corresponding antigens. Specifically, if a major source of defective ribosomal products is pre-mature stop in translation, an overrepresentation of CD8+ T-cell epitopes in the N-terminal portion of antigens would be expected. In contrast, if downstream initiation is a major source of defective ribosomal products, C-terminal portions of antigens would be a dominant source of epitopes. In this study, we systematically assess positional bias of epitopes in viral antigens, taking advantage of the large set of immune epitope data available in the Immune Epitope Database. We demonstrate that there is a small degree of positional skewing detectable in the epitope distribution. Epitopes from both ends of antigens tend to be slightly underrepresented, which suggests that both pre-mature stops in translation and downstream initiation play an equal but minor role in shaping the overall viral epitope repertoire.