T-cell costimulatory receptors (CD28, CD2, and LFA-1) (TRICOM receptors)

The T-cell costimulatory receptors CD28, CD2, and LFA-1 (Integrin alpha-L/beta-2) constitute a functional triad of molecules on the surface of T-lymphocytes that are essential for robust immune activation. In the context of TRICOM (TRIad of COstimulatory Molecules) immunotherapy, these receptors are specifically engaged by their ligands—B7-1 (CD80), ICAM-1 (CD54), and LFA-3 (CD58)—which are co-expressed on antigen-presenting cells (APCs) via viral vectors (Hodge et al., 1999, Cancer Research). CD28 provides the primary costimulatory signal required for T-cell survival and IL-2 production, while CD2 and LFA-1 act as adhesion and signaling molecules that stabilize the immunological synapse and lower the threshold for T-cell receptor activation (Madan et al., 2010, Expert Opin Biol Ther). This synergistic interaction is designed to overcome tumor-induced immunosuppression and enhance the frequency and avidity of tumor-specific cytotoxic T-lymphocytes. Therapeutic agents like PROSTVAC and PANVAC utilize this mechanism to treat prostate and gastrointestinal cancers, respectively, by presenting tumor-associated antigens alongside the TRICOM ligands to the immune system (Gulley et al., 2019, J Clin Oncol).

Other names

CD28, CD2, and LFA-1 triadTRICOM-engaged receptorsT-cell costimulatory triadCD28/CD2/LFA-1 complex

Synergistic engagement of CD28, CD2, and LFA-1 by TRICOM ligands (B7-1, ICAM-1, LFA-3) expressed on APCs provides essential costimulatory and adhesion signals that lower the threshold for T-cell activation and enhance anti-tumor effector functions.