T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

ABSTRACT

T cells are extensively trained on ‘self’ in the thymus and then move to the periphery, where they seek out and destroy infections and regulate immune response to self-antigens. T cell receptors (TCRs) on T cells’ surface recognize T cell epitopes, short linear strings of amino acids presented by antigen-presenting cells. Some of these epitopes activate T effectors, while others activate regulatory T cells. It was recently discovered that T cell epitopes that are highly conserved on their TCR face with human genome sequences are often associated with T cells that regulate immune response. These TCR-cross-conserved or ‘redundant epitopes’ are more common in proteins found in pathogens that have co-evolved with humans than in other non-commensal pathogens. Epitope redundancy might be the link between pathogens and autoimmune disease. This article reviews recently published data and addresses epitope redundancy, the “elephant in the room” for vaccine developers and T cell immunologists.

KEYWORDS:

• T cell epitope
• regulatory T cell
• cross-conservation
• T cell receptor
• TCR
• TCR degeneracy
• molecular mimicry
• autoimmune disease
• immunoinformatics
• Guillain-barré syndrome
• narcolepsy
• multiple sclerosis
• vaccine
• off-target effects
• HIV
• HCV
• H7N9
• influenza vaccine
• cancer vaccine
• virus
• bacteria
• parasite

Financial & competing interests disclosure

A De Groot and W Martin are founders and majority owners of EpiVax, Inc. a biotechnology company that provides access to immunoinformatics tools and designs vaccines for commercial clients. L Moise holds options at EpiVax, Inc. Authors S Beseme, F Kibria, and F Terry are employees of EpiVax, Inc. Due to this relationship with EpiVax, the six authors acknowledge that there is a potential conflict of interest inherent in the publication of this manuscript, and assert that they made an effort to reduce or eliminate that conflict where possible. The authors thank Guilhem Richard and Genevieve De Groot for their contribution to the illustrations. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.