T Cell Receptor (TCR) Structure and Function

• Early T cell receptor (TCR) studies faced challenges as TCRs are membrane-bound and not soluble like B cell receptors.
• The T cell antigen recognition molecule is a heterodimer with a single variable region.
• The genomic organization of the TCR mirrors the B cell receptor, crucial for the adaptive immune response.
• Alpha/Beta TCRs exhibit high specificity.
• Gamma/Delta T cells identify specific PAMPs, acting more like innate immunity components.

TCR Structure

• TCRs mainly consist of two chains: alpha and beta.
• The antigen-binding site is located in the hypervariable region.
• Constant domains anchor the molecule to the cell membrane for intracellular signaling.

Alpha/Beta vs. Gamma/Delta T Cells

• Gamma/Delta T cells identify specific antigen classes and operate akin to innate immunity.
• Expanding T cell functional roles is advantageous for overcoming infections, given the immune system's complexity.
• Gamma/Delta T cells are fewer in circulation compared to Alpha/Beta T cells.
• Gamma/Delta T cell specificity targets pathogens commonly encountered.

T Cell Co-receptors: CD4 and CD8

• CD4 and CD8 co-receptors are vital for TCR function and MHC interaction.
• Alpha/Beta TCRs use CD4 or CD8 co-receptors.
• CD4 is used by T helper cells recognizing antigens presented by MHC class II.
• CD8 is used by cytotoxic T cells recognizing antigens presented by MHC class I.
• Gamma/Delta TCRs don't need CD4 or CD8 co-receptors.
• Gamma/Delta T cells resemble innate immune cells, recognizing non-peptide antigens without classical MHC presentation.
• Gamma/Delta T cells function independently of CD4/CD8 and target lipids and stress molecules presented by non-classical MHC molecules.
• These cells are innate-like, involved in rapid immune responses, unlike Alpha/Beta T cells, that are adaptive, and dependent on co-receptors like CD4 and CD8.

TCR Complexes and Signaling

• TCR signaling is facilitated by the CD3 complex, including CD247 containing ITAMs.

Functional Differences in TCRs

• Gamma/Delta TCRs identify specific antigen classes and function like innate immunity.
• Gamma/Delta T cells diversify T cell immunological function.
• There are fewer circulating gamma/delta T cells than alpha/beta cells.
• Gamma/Delta T cell specificity can target commonly encountered pathogens.
• Alpha, beta TCR and gamma, delta TCR have different functional chains.

TCR Alpha/Beta Structure

• TCR alpha/beta consists of an alpha chain (49 kDa) and a beta chain (43 kDa).
• Each chain has two extracellular domains, a transmembrane portion, and a cytoplasmic tail.
• The outermost domain is the variable domain (V), and the other is the constant domain (C).
• Both domains are stabilized by internal disulfide bonds.
• The variable domains of alpha and beta chains create the antigen-binding site.
• TCRs need assistance from a complex of proteins (gamma, delta, epsilon, and zeta) that transmit signals to the nucleus for T cell activation because the cytoplasmic tail of the TCR is so short
• CD3 heterodimers (delta/epsilon and gamma/epsilon) and the zeta chains form this protein complex.

B Cell Receptor (BCR)

• B cell receptor (BCR) was identified and studied due to its soluble properties, like immunoglobulin molecules.
• Membrane Ig associates with the BCR structure.
• The disulfide-linked heterodimer Ig alpha and Ig beta forms the BCR complex.
• The BCR has antigen-binding variable regions and constant regions.
• The Ig alpha/Ig beta heterodimer stabilizes the BCR and enables signal transduction.

BCR Structure

• The BCR has a light chain, heavy chain, and two variable regions.
• Ig alpha/Ig beta anchors the immunoglobulin molecule through the lipid bilayer and facilitates signal transduction via ITAMs.
• The BCR has two antigen-binding sites.
• The BCR is stabilized by the Ig alpha/Ig beta heterodimer, which also conducts signal transduction.

BCR vs TCR

• B and T cell receptor comparison is essential for understanding structural importance, receptor activation, and immune response.
• Differences between BCR and TCR include the number of variable regions, receptor solubility, and specificity.
• Immunoglobulins on the B cell surface act as BCRs, each with two antigen recognition regions.
• T cells have various membrane-bound TCRs.
• Each T cell produces a TCR with a higher affinity for antigen bound to MHC molecules than for soluble antigen.
• The BCR and TCR anchor via accessory molecules (Ig alpha/Ig beta or CD3 complex), facilitating signal transduction and receptor activation.

B Cell Receptor (BCR) vs T Cell Receptor (TCR)

• TCRs contain a single antigen-binding site and bind to peptide antigens presented on MHCs.
• BCRs consist of a surface immunoglobulin with two antigen-binding sites, including heavy and light chains.
• Transmembrane protein (Ig beta and Ig alpha heterodimer linked to ITAM chains) transmits signals inside the cell

BCR vs. TCR Comparison

Structure

• BCR:
  • It is a membrane-bound immunoglobulin (Ig).
  • It comprises two identical heavy chains and two identical light chains, forming a Y-shape.
  • Features a transmembrane region for attachment to the B cell membrane.
  • The tips of the Y contain variable regions for specific antigen binding.
• TCR:
  • It is a transmembrane protein.
  • It is composed of α and β chains (or γ and δ chains), forming a heterodimeric structure.
  • It is embedded in the T cell membrane using a transmembrane region.
  • The tips of the TCR chains contain variable regions responsible for antigen recognition.

Function

• BCR:
  • B cells recognize antigens directly, including proteins, carbohydrates, and lipids.
  • It is expressed on the surface of B cells.
  • The function of the BCR Initiates B cell activation upon antigen binding to variable regions.
  • Differentiation Outcome of activated B cells into plasma cells, which produce antibodies (secreted BCR forms) that neutralize or eliminate pathogens.
• TCR:
  • It recognizes antigens presented by major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs).
  • It is expressed on the surface of T cells.
  • TCR plays a central role in T cell activation through binding to antigen-MHC complexes.
  • Differentiation Outcome of activated T cells into effector T cells with different functions, such as cytotoxic T cells (CD8+) or helper T cells (CD4+).

####Antigen Interaction

• BCR:
  • It binds directly to antigens without needing antigen presentation.
• TCR:
  • It requires antigen presentation by MHC molecules (MHC restriction).
  • CD4+ T cells recognize antigens presented by MHC class II.
  • CD8+ T cells recognize antigens presented by MHC class I.