T cells play a central role in shaping the adaptive immune system. Against non-self antigens with pathogenic threat, T cells should develop immunity. On the other hand, T cells are supposed to become tolerant to self antigens or innocuous environmental antigens. Many immunological disorders such as immunodeficiency, autoimmune diseases, and allergies are caused by T cells that fail to obey the above rules.

T cells are guided by two kinds of sensors during immune reaction to make decisions: the antigen receptor (TCR) and cosignaling receptors. Engagement of TCRs with cognate antigens presented by MHC molecules provides a specificity signal. Along with TCR, positive cosignals (also known as costimulation) and negative cosignals are given to T cells while T cells interact with antigen presenting cells or target cells. Positive cosignals amplify whereas negative cosignals inhibit TCR signals. A balance between positive and negative cosignals influences T cell activation, differentiation, survival, and ultimately immunity vs. tolerance. Thus, understanding the mechanisms of T cell cosignaling should facilitate development of tools to boost immunity or suppress unwanted immune reactions.

Members of the CD28 family cosignaling receptors and their ligands (members of B7 family) are known to play crucial roles in T cell immunity and tolerance. Dr. Suh’s laboratory is investigating the molecular and cellular mechanisms of CD28-B7 family of T cell cosignaling molecules using a panel of knockout, knockin, and transgenic mice. Impacts of altered T cell cosignaling are analyzed at the biochemical or cellular levels using immune cells isolated from the mice. The consequences of altered cosignaling in overall immune reactions in mice are examined in the context of infection, cancer, autoimmunity, and allergy.

Recently Dr. Suh’s research team demonstrated that a positive cosignaling receptor of the T cells, Inducible Costimulator (ICOS), facilitates generation of helper T cells by potently activating a signal transducer phosphoinositide 3-kinase (published in PNAS). This study shed new light on as to how multiple cosignaling receptors come together in a timely manner to orchestrate T cell differentiation to optimize antibody responses (see Model).