T Cell Receptor
Overview
The T cell receptor (TCR) is a protein complex found on the surface of T cells, a type of white blood cell that plays a crucial role in the immune system. The TCR is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of great importance to the immune response, leading to T cell activation and subsequent immune reactions.
Structure
The T cell receptor is a heterodimeric protein complex, most commonly composed of an alpha (α) and a beta (β) chain, although in some cases gamma (γ) and delta (δ) chains are used. These chains are covalently linked by a disulfide bond, and each chain has a constant and a variable region. The variable region of each chain is involved in recognizing antigens.
The α and β chains each have a single extracellular variable domain, followed by a constant domain, a transmembrane domain, and a short cytoplasmic tail. The variable domain is responsible for recognizing antigens, while the constant domain aids in the expression of the TCR on the cell surface and interacts with other components of the T cell.
Antigen Recognition
The T cell receptor recognizes a specific antigenic peptide sequence presented by the MHC molecule on the surface of an antigen-presenting cell (APC). This recognition is crucial for the activation of the T cell and the initiation of an immune response.
The TCR recognizes the antigenic peptide in the context of the MHC molecule, meaning that it recognizes both the peptide and the MHC molecule. This is known as MHC restriction. The TCR does not recognize free-floating antigens, but rather antigens that have been processed and presented by an APC.
T Cell Activation
The binding of the TCR to the antigen-MHC complex on an APC triggers a series of intracellular signaling events that lead to T cell activation. This process is known as T cell receptor signaling.
The TCR itself does not have any intrinsic signaling capabilities. Instead, it relies on associated signaling molecules, such as the CD3 complex and the ζ-chain, to transmit the activation signal into the cell. These molecules contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domains, which become phosphorylated upon TCR engagement.
Diversity
The diversity of the T cell receptor repertoire is generated through a process known as V(D)J recombination, which occurs during T cell development in the thymus. This process involves the random rearrangement of gene segments in the TCR gene locus, leading to a vast number of possible TCR combinations and allowing for the recognition of a wide array of antigens.
The diversity of the TCR repertoire is further increased by junctional diversity, which is the addition or deletion of nucleotides at the junctions between gene segments during V(D)J recombination.