title: A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Susanne G
authors.initials: SG
authors.lastname: Oberle
authors.affiliation: Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Layane
authors.initials: L
authors.lastname: Hanna-El-Daher
authors.affiliation: Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Chennupati
authors.affiliation: Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Enouz
authors.affiliation: Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Scherer
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19024, Seattle, WA 98109, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Prlic
authors.affiliation: Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland. Electronic address: dietmar.zehn@tum.de.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D060085:Coinfection / Q000276:immunology; D003141:Communicable Diseases / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007156:Immunologic Memory; D007249:Inflammation / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte
keywords: T cell activation threshold; cytotoxic T cells; secondary immune responses; strength of TCR stimulation