Immune Checkpoints of the B7 Family. Part 1. General Characteristics and First Representatives: B7-1, B7-2, B7-H1, B7-H2, and B7-DC

Abstract

T-cell response along with humoral response compose the basis of acquired immunity. Effective activation of T lymphocytes requires at least two signals. The first signal is provided by the interaction of T-cell receptor with antigenic peptide in the context of major histocompatibility complex molecules (I or II class). The second signal required for T cell activation, proliferation and differentiation is delivered by molecules called “immune checkpoints” which determine the polarity, effectiveness and termination of the immune response. The immune checkpoint group consist of around 70 members. The first discovered molecules that control immune response belong to the B7 family of cell membrane proteins. The classical two-signal model for T cell activation was developed with their implication. Immune checkpoints have gained popularity after successful clinical trials of antibodies blocking CTLA-4 and PD-1 receptors (immune checkpoint inhibitors), in which the tremendous antitumor effects were demonstrated. Considering the importance of the immune checkpoints in therapeutic regulation of antitumor immunity, in this review we describe the functional properties of all known today molecules of the B7 family. The first part of our review discusses the structural features, functions and therapeutic applications of B7-1, B7-2, B7-H1, B7-H2, B7-DC, and their receptors.