Biology · MU Sofia

28. Cell-mediated immunity. Molecules of cell-mediated immunity: T-cell receptor (TCR). (MHC).

Explains the T-cell receptor as a membrane-bound heterodimer of alpha and beta chains, covering its domain layout, how it differs from antibodies, and its linkage to CD3 and zeta for signal transduction. It then describes MHC class I and II genes, tissue distribution, and peptide-binding clefts, with a visual analogy for the cleft shape, and closes with how T-cells recognise processed peptides in MHC restriction and the roles of the CD4 and CD8 co-receptors.

Inside: 5 sections · 3 labelled pictures · 5 min

Topic 28 of 64 in the MU Sofia syllabus for Biology (Dental Medicine, Year 1). The free AceMed note covers it in 5 sections, about 763 words (5 min of reading).

In this note

  1. Introduction
  2. Signal Transduction by TCR
  3. Major Histocompatibility Complex (MHC)
  4. Structure of MHC
  5. Epitopes Recognized By T-Cells

Introduction

Cell Receptors (TCR) Overview

  • Function of TCR
  • Role in Immunity: T-cell receptors are crucial for cell-mediated immunity, which is the primary function of T-lymphocytes (T-cells).
  • Antigen Recognition: TCRs enable T-cells to specifically recognize antigens through a surface receptor that belongs to the immunoglobulin superfamily of proteins.
  • Cell Surface Receptor: Unlike antibodies, the TCR is always a membrane protein and never detaches from the cell surface.
  • Types of TCR
  • TCR1: Found in a small subset of T-cells (<10%) located beneath mucosal epithelia and skin, involved in local immunity. This type is less studied and not the focus here.
  • TCR2: The more commonly discussed TCR, present on the majority of T-cells.
  • Structure of TCR
  • Composition: TCR is a heterodimer consisting of α- and β-chains linked by disulfide bonds.
  • Chain Orientation: The N-terminus of each chain is extracellular, while the C-terminus resides within the cytoplasm.
  • Glycosylation: Like most membrane proteins, TCR2 is glycosylated to enhance functionality.
  • Domain Arrangement: Each chain features two domains:
  • Constant Domain: Closer to the cell membrane and remains the same across different TCRs.
  • Variable Domain: Located at the N-terminus, varies among T-cells, allowing the recognition of different antigens. This domain contains hypervariable or complementary-determining regions (CDRs), which form the antigen-binding site when paired (V-α and V-β).
  • Comparison with Antibodies
  • Size: TCRs are considerably smaller than antibodies, analogous to an isolated Fab fragment of an antibody.
  • Functionality Difference:
  • Antibodies: Can be secreted outside B-cells and act in soluble form. They include an Fc fragment that serves important adaptor functions.
  • TCRs: Remain membrane-bound, focusing solely on transmitting a signal inside the cell when an antigen is bound. TCRs lack a large constant part because they do not need to function outside the cell or perform secondary roles like antibodies.

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