A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire

• Main Authors: Susanne G. Oberle, Layane Hanna-El-Daher, Vijaykumar Chennupati, Sarah Enouz, Stefanie Scherer, Martin Prlic, Dietmar Zehn
• Format: Article
• Language: English
• Published: Elsevier 2016-10-01
• Series: Cell Reports
• Subjects: T cell activation threshold; cytotoxic T cells; secondary immune responses; strength of TCR stimulation
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124716313286

Many infections are caused by pathogens that are similar, but not identical, to previously encountered viruses, bacteria, or vaccines. In such re-infections, pathogens introduce known antigens, which are recognized by memory T cells and new antigens that activate naive T cells. How preexisting memory T cells impact the repertoire of T cells responding to new antigens is still largely unknown. We demonstrate that even a minimum epitope overlap between infections strongly increases the activation threshold and narrows the diversity of T cells recruited in response to new antigens. Thus, minimal cross-reactivity between infections can significantly impact the outcome of a subsequent immune response. Interestingly, we found that non-transferrable memory T cells are most effective in raising the activation threshold. Our findings have implications for designing vaccines and suggest that vaccines meant to target low-affinity T cells are less effective when they contain a strong CD8 T cell epitope that has previously been encountered.