This invention provides compounds for modulating T-cell pathways and subsequent immunity.
Autoimmune diseases are characterized by the activation of T-cells against self-antigens. The T-cells then destroy the cells producing the antigens. The diseases and conditions associated with this immune response are generally associated with a specific protein on the cell surface: major histocompatibility complex class II molecules (MHC-II).
A defining stage in the immune response occurs when the T-cells differentiate into type 1 and type 2 helper cells. Activation of either pathway requires a two-signal mechanism. Signal-1 occurs when the T-cell antigen receptor recognizes the peptide-MHC-II complex on the antigen cell surface. Signal-2 occurs upon binding of Signal-2 receptors to their ligands on the surface of the antigen presenting cells.
The invention can be applied to elicit a desired immune response without affecting the immune response from other antigens.
The core invention surrounds a novel AB peptide, wherein the A can bind with a major histocompatibility complex on an antigen-presenting cell and B can bind with Signal-2 receptor on an antigen-presenting cell. This design creates a new class of immunotherapeutic peptides aptly termed bifunctional peptide inhibitors. As a result, the invention provides a method of modulating T-cell pathways and subsequent immunity in a very specific manner such that the product of this invention targets only specific disease-associated populations of these cells.
The invention embodies a set of specific tags that can easily be connected to each other through a chemical moiety that has the ability to vary in length allowing a tunable system for controlling T-cell differentiation.
Unlike current T-cell inhibitors, the invention allows for both Signal-1 and Signal-2 binding, completing the two-fold mechanism necessary to alter T-cell differentiation. This allows for a target specific approach to differentiation, leaving the immune cells not targeted to remain unaffected.