HVEM-derived peptides as inhibitors of HVEM/LIGHT complex formation

T cells are important targets for therapeutic intervention in many diseases. Modifying T cell activation via immune checkpoints plays a central role in such approaches. The HVEM/LIGHT complex is one of the stimulatory immune checkpoints involved in T cell activation, and binding of these proteins results in proliferation and development of effector functions of T cells. In patients suffering from autoimmune diseases and in transplant recipients it is desirable to suppress immune responses. This could be achieved by blocking the HVEM and LIGHT interactions. Our studies concern blockage of the formation of the HVEM/LIGHT complex using peptides. To design the inhibitors of this interactions, we relied on the amino acid sequence and the structure of the LIGHT-binding fragments of HVEM. We measured the affinity of designed peptides to LIGHT using SpS technique and tested their ability to inhibit the formation of the HVEM/LIGHT complex using ELISA and cellular studies. That led to the identification of two peptides, namely CRD2e_K54E and CRD2(39-73)e that strongly bind to LIGHT and possess blocking capacities towards HVEM/LIGHT complex formation. Obtained data indicate that HVEM-derived peptides could form the basis for future therapeutics, highlighting the need for further exploration of their immunomodulatory potential.