T cell receptors (TCRs) are critical components of the adaptive immune system. They are responsible for recognizing antigens, which are specific molecules or fragments from pathogens (like viruses and bacteria) that trigger an immune response. Understanding TCRs is essential for grasping how T cells function in immune surveillance and response.
Structure of T Cell Receptors
- TCRs are heterodimeric proteins, typically composed of two different chains: the alpha (α) and beta (β) chains. Some T cells, known as γδ T cells, possess gamma (γ) and delta (δ) chains instead.
- Variable regions : The variable regions of the TCR chains (Vα and Vβ) are responsible for the specificity of antigen recognition. These regions exhibit a high degree of variability, allowing for the recognition of a vast array of antigens.
- Constant Regions: The constant regions (Cα and Cβ) provide structural stability and are less variable.
- Antigen Binding Site: The antigen binding site is formed by the combination of the variable regions of the α and β chains. This site is highly specific for a particular peptide-MHC (Major Histocompatibility Complex) complex.
- Transmembrane Domain: Each TCR has a transmembrane domain that anchors the receptor in the T cell membrane.
- Intracellular Signaling Motifs: TCRs do not directly transmit signals into the cell. Instead, they associate with CD3 and ζ (zeta) chains, which contain immunoreceptor tyrosine-based activation motifs (ITAMs) crucial for signal transduction.
TCR Gene Rearrangement
The diversity of TCRs arises from a process called somatic recombination during T cell development in the thymus.
Mechanism:
- Gene Segments: The TCR genes are composed of multiple segments: V (variable), D (diversity), and J (joining) segments.
- Recombination: Enzymes known as recombination activating genes (RAG-1 and RAG-2) facilitate the rearrangement of these gene segments, leading to the production of unique TCRs.
- Clonal Selection: During T cell maturation, T cells with non-functional or self-reactive TCRs are eliminated, ensuring that only T cells capable of recognizing foreign antigens remain.
TCR and Antigen Recognition
TCRs recognize antigens primarily in the form of peptide fragments presented by MHC molecules on the surface of antigen-presenting cells (APCs).
- Types of MHC:
- MHC Class I: Presents endogenous peptides (from intracellular proteins) to CD8+ cytotoxic T cells.
- MHC Class II: Presents exogenous peptides (from extracellular proteins) to CD4+ helper T cells.
- Interaction Process:
- Peptide Binding: The TCR recognizes a specific peptide that is bound to an MHC molecule. This interaction is highly specific and is a key determinant of T cell activation.
- Co-stimulation: In addition to TCR engagement, T cells require secondary signals (co-stimulatory signals) from APCs for full activation. CD28 on T cells interacts with B7 on APCs, providing the necessary co-stimulatory signal.
- T Cell Activation: Once a T cell recognizes its specific antigen-MHC complex and receives co-stimulatory signals, it undergoes a series of activation events:
- Tyrosine Phosphorylation: The ITAMs in the CD3 and ζ chains become phosphorylated, initiating a signaling cascade.
- Cytokine Production: Activated T cells produce various cytokines that mediate immune responses and further stimulate other immune cells.
- Proliferation and Differentiation: Activated T cells proliferate and differentiate into effector T cells (e.g., cytotoxic T cells, helper T cells) and memory T cells for long-term immunity.
| Feature | B Cell Receptors (BCRs) | T Cell Receptors (TCRs) |
| Structure | Membrane-bound immunoglobulins (antibodies) consisting of two heavy and two light chains; can also be secreted as antibodies | Heterodimeric proteins made up of an alpha (α) and a beta (β) chain; no secreted form |
| Antigen Recognition | Bind directly to free-floating antigens (proteins, carbohydrates, lipids) in their native form | Recognize processed peptides presented on MHC molecules; only bind linear peptide sequences |
| Types of Cells | Found on B lymphocytes; responsible for humoral immune response | Found on T lymphocytes (CD4+ helper and CD8+ cytotoxic T cells); crucial for cell-mediated immunity |
| Activation Mechanisms | Requires two signals: binding of BCR to antigen and additional signals from T helper cells (e.g., CD40/CD40L interaction) | Requires recognition of peptide-MHC complex by TCR and co-stimulatory signals (e.g., CD28 binding to B7) |
| Response to Antigen | Proliferate and differentiate into plasma cells (secreting antibodies) and memory B cells for long-term immunity | Proliferate and differentiate into effector cells (e.g., cytotoxic T cells, helper T cells) and memory T cells |
| Function in Immunity | Produce antibodies that neutralize pathogens, facilitate opsonization, and activate complement | Recognize and eliminate infected or cancerous cells; help orchestrate immune responses and assist B cells |
T cell receptors are essential for the adaptive immune response, enabling T cells to recognize and respond to a diverse range of pathogens. Understanding the structure, function, and signaling pathways associated with TCRs is vital for developing immunotherapies and vaccines.