Development of effective vaccines or antigen-specific immunotherapies for allergies, autoimmunity, cancers and chronic inflammation could benefit from analytical models capable of accurately predicting the outcome of immunotherapeutic interventions. A few recent notable successes notwithstanding, failure to develop such models has frustrated translation of experimental research findings into proven clinical applications.

At Tregeutix we believe only a cardinal departure from current thinking about immune response regulation could promote a breakthrough in the form of novel predictable analytical models able to accurately interpret available scientific and clinical data.

SPIRAL (Specific ImmunoRegulatory Algorithm) is a unique, first-in-kind discovery framework with the capacity to accurately predict behavior of adaptive immune responses in an antigen-specific manner. Present dogma dictates the adaptive immune system makes two separate decisions when responding to a new antigen,

• Decision 1, commonly referred to as self-nonself discrimination, about whether to respond or to tolerate a new antigen, and
• Decision 2, referred to as immune response effector choice regulation, about the most effective type of immune response.

However, by flipping the concept of antigen cross-reactivity and recognizing it as the proper foundation of immune response regulation rather than a "programming glitch", SPIRAL reveals that contrary to long-held views, self-nonself discrimination and immune response effector choice regulation are one and the same process controlled by antigen-specific Foxp3+ regulatory T cells maintained by specific members of microbiota. The SPIRAL framework represents the periodic table of Treg epitopes. Its predictive potential could transform the immunotherapy landscape by rightfully placing center-stage the immune system's fundamental attribute of cross-reactivity.

By simplifying systematic discovery of Foxp3⁺ regulatory T cell epitope specificities and corresponding microbiota species that maintain them, SPIRAL could help develop effective therapies to protect against allergies, autoimmunity and chronic inflammation, and determine effectiveness of vaccines to natural infections and tumors.