Abstract: The present disclosure relates to methods and compositions useful for initiating and propagating ICOS-mediated signaling. In particular, the present disclosure provides three peptide motifs which promote ICOS binding and whose ablation leads to modulated ICOS signaling and modulated signaling mediated by TBK1, IRF4, IKK?, or TBKBP1. The binding of these peptide motifs or the addition of such motifs as co-stimulatory agents leads to modulated immune responses, and provides new and unexpected therapies for neurodegenerative, autoimmune, metabolic, cancer inflammatory, or immunodeficiency conditions, diseases, or disorders.

Abstract: The present disclosure relates to methods and compositions useful for initiating and propagating ICOS-mediated signaling. In particular, the present disclosure provides three peptide motifs which promote ICOS binding and whose ablation leads to modulated ICOS signaling and modulated signaling mediated by TBK1, IRF4, IKK?, or TBKBP1. The binding of these peptide motifs or the addition of such motifs as co-stimulatory agents leads to modulated immune responses, and provides new and unexpected therapies for neurodegenerative, autoimmune, metabolic, cancer inflammatory, or immunodeficiency conditions, diseases, or disorders.

Abstract: The invention relates to compositions, methods and uses of inhibitors of binding between PKC? and CD28, and modulating an undesirable or aberrant immune response, disorder or disease, an inflammatory response, disorder or disease, inflammation or an autoimmune response, disorder or disease. Compositions include inhibitors of binding between PKC? and CD28, which include, among others, PKC?, CD28 and Lck sequences, subsequences, variants and modified forms, and polymorphisms.

Abstract: Compounds, uses and methods for modulating an immune response are provided. In particular, modulating the interaction of PKC? with CTLA-4 can modulate an immune response. For example, modulating activity or expression of PKC?, and/or modulating activity or expression of CTLA-4, can be used to modulate interaction of PKC? with CTLA-4, thereby modulating an immune response.

Abstract: The invention relates to compositions, methods and uses of inhibitors of binding between PKC? and CD28, and modulating an undesirable or aberrant immune response, disorder or disease, an inflammatory response, disorder or disease, inflammation or an autoimmune response, disorder or disease. Compositions include inhibitors of binding between PKC? and CD28, which include, among others, PKC?, CD28 and Lck sequences, subsequences, variants and modified forms, and polymorphisms.