Our science is built on elucidating the fundamental mechanism of peripheral self-nonself discrimination, after thymic negative selection, in the context of immune self-tolerance.
For many decades, the mechanism governing self-tolerance, i.e. self-nonself discrimination, of one’s immune system has been considered by many as a Holy Grail of immunology. Conceptually speaking, selective control of unwanted immune responses could be achieved by induction of “antigen-specific tolerance”, provided that the specific antigens eliciting these responses have been identified. However, for decades, it has always been a tremendous challenge to identify the exact pathogenic peptide/s for any given human autoimmune diseases, or specific allo-antigen peptide/s responsible for graft rejection. In reality, it has been extremely difficult to pinpoint any definitive disease-specific and disease-causing pathogenic antigens for any human autoimmune diseases.
Avotres has identified a novel mechanism of action centered on Qa-1/HLA-E restricted CD8+ Treg (Q/E CD8+ Treg), and its function to specifically suppress self-reactive T cell pool to achieve self-tolerance. This mechanism is named by our researchers as "Avidity Model of Peripheral T Cell Regulation”, in which self-tolerance via self-nonself discrimination is achieved by peripheral immune regulation after normal central thymic selection is completed. We envision that the immune system achieves self-nonself discrimination during adaptive immunity, not by recognizing the structural differences between self versus foreign antigens, but rather by perceiving the avidity of T cell activation.
Immunological disorders across three major clinical areas: autoimmune diseases, transplantation and certain tumors, have been found to be caused and/or affected by the functional status of the Q/E CD8+ Tregs in a newly identified mechanism of “peripheral self-nonself discrimination”. By targeting the root cause of autoimmune diseases and transplantation, and addressing new immuno-oncology targets for certain tumors, Avotres aims to transform therapeutic intervention options for the broad spectrum of these devastating conditions.