Conjugate compositions that combine a functionalized I-domain peptide covalently bound to multiple signal-1 blocking moieties to reduce type-1 immune responses.
Autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and type-I diabetes are examples of conditions where the host immune system attacks host cells and tissues. These diseases are based on normal antigens causing T-cells to differentiate into type 1 helper cells that destroy healthy cells and tissues. Present treatments can slow the progression but become ineffective when epitope spreading causes a different antigen to differentiate T-cells into type-1 helper cells. The present invention provides a method for appending multiple Signal-1 antigens to a Signal-2 antigen to prevent epitope spreading from increasing the progression of autoimmune diseases.
The invention provides conjugate compounds that can treat and slow the progression of autoimmune diseases.
The core invention provides a method for adding a peptide sequence to an epitope specific for a Signal-2 antigen receptor. The peptide contains multiple lysine residues that are ultimately modified. The modified lysine residues contain moieties that allow for easy addition of additional peptide units. These added peptide units consist of multiple epitopes that can bind to different possible Signal-1 receptors on naive T-cells. This creates a multifunctional antigen conjugate compound capable of inhibiting Signal-1 and Signal-2 causing T-cells to differentiate into type 2 helper cells creating an anergic response in the area of the disease.
The invention creates a two-fold process for inhibiting the differentiation of type 1 helper cells that are the primary culprit in the progression of autoimmune diseases.
The current monofunctional and bifunctional peptides that are used to treat autoimmune diseases work with relatively good efficiency in the initial treatment such diseases. Their effectiveness decreases when a different antigen activates Signal-1 through epitope spreading. The current invention solves this problem through the ability to amend multiple Signal-1 blocking epitopes to a single Signal-2 epitope. This allows for a variety of activating epitopes to be blocked from activating Signal-1 and overcome the problem of epitope spreading.