T cell receptor (TCR)

TCR
• The TCR is a complex of transmembrane proteins that are unique to each T cell
and are responsible for recognizing antigens presented by MHC molecules on
antigen-presenting cells (APCs).
• The TCR is composed of two different protein chains, alpha and beta, or gamma
and delta, that are associated with each other to form the TCR complex.
• The TCR has a highly diverse and combinatorial repertoire, which allows T cells to
recognize a wide range of antigens. The specificity of the TCR for antigen
recognition is determined by the complementarity-determining regions (CDRs) of
the TCR, which interact with the antigen presented by MHC molecules on
antigen-presenting cells (APCs).
• When a T cell encounters an APC presenting an antigen that matches the TCR,
this interaction can activate the T cell and initiate an immune response. The
specificity of the TCR for antigen recognition is crucial for the proper functioning
of the immune system, as it ensures that T cells only respond to antigens that
pose a threat to the body.
Important aspects of TCR
• Each T cell has TCR of only ONE specificity
• This is due to a process called allelic exclusion, which occurs during T cell development in the thymus.
• Allelic exclusion ensures that each T cell expresses only one functional TCR on its surface, allowing for the
proper recognition and response to antigens.
• αβ TCR recognizes Ag only in the context of cell-cell interaction and in the correct MHC context
• Γδ TCR recognizes Ag in an MHC-independent manner
• Response to certain viral and bacterial Ag
• During T cell development, the TCR genes undergo recombination to generate a diverse repertoire of TCRs.
However, as the T cell matures, only one TCR gene is expressed, while the other TCR genes are silenced. This
ensures that each T cell has a unique TCR with a single specificity for a particular antigen, allowing the T cell
to specifically recognize and respond to that antigen.
• Allelic exclusion is a crucial process in the functioning of the immune system, as it ensures that T cells are
able to recognize a wide range of antigens and respond appropriately to different threats.
 Role of TCR in immune response
• Surface molecule on T cells
• Recognize Ag presented in MHC context
• Two types of TCR
• α β: predominant in lymphoid tissues
• γ δ: enriched at mucosal surfaces
• Heterodimer
• α and β chains, approx. equal length
• Regions
• Short cytoplasmic tail- cannot transduce activation
signal
• Transmembrane with hydrophobic AAs
• Both α and β have a variable (V) and constant (C)
region
• V region is hypervariable, determines Ag specificity
Genetic basis for receptor generation
• Accomplished by recombination of V, D and J gene segments
• TCR β chain genes have V, D, and J
• TCR α chain genes have V and J
TCR and CD3 complex
• TCR is closely associated with CD3 complex
• Group of 5 proteins
• Commonly called “invariant” chains of TCR
• Role of CD3 complex
• CD3 necessary for cell surface expression of TCR
• transduces signal after Ag interaction with TCR
Key steps in T cell activation
• APC must process and present peptides to T cells
• T cells must receive co-stimulatory signal
• Accessory adhesion molecules stabilize binding of TCR and MHC
• Signal from cell surface is transmitted to nucleus
• Cytokines produced help drive cell proliferation
 The “immunological synapse”
• TCR-MHC interaction is not strong
• Accessory molecules stabilize interaction
• CD4/MHC class II or CD8/MHC class I
• CD2/LFA-3: The interaction between CD2 on T cells and LFA-3 (Lymphocyte
Function-associated Antigen 3) on APCs is important for the activation and
proliferation of T cells.
• LFA-1/ICAM-1- The interaction between LFA-1 (Lymphocyte Function-associated
Antigen 1) on T cells and ICAM-1 (Intercellular Adhesion Molecule 1) on APCs is
critical for the adhesion and migration of T cells during an immune response.
• Specificity for Ag is solely in TCR
• Cytokines change expression levels
• For example, cytokines such as interleukin-2 (IL-2) can upregulate the expression of
co-stimulatory molecules, such as CD28 and CD137, on T cells, enhancing T cell
activation and proliferation. Conversely, cytokines such as interferon-gamma (IFN-γ)
can downregulate the expression of adhesion molecules, such as LFA-1, on immune
cells, reducing their ability to adhere to other cells and tissues.
• Co-stimulation is also necessary for activation of T cells
• CD28/CD80 or CD86-CD28 is a co-stimulatory receptor expressed on T cells, while CD80 (also known as
B7-1) and CD86 (also known as B7-2) are co-stimulatory ligands expressed on antigen-presenting cells (APCs).

• CTLA-4 on T cells can also ligate CD80/CD86 -

• Inhibitory signal
• downregulation
Thank you