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Understanding T Cell Receptor Signaling Pathways and Their Role in Immune Response

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finna
22 diapositives · 357 Views · Jul 24, 2014

This article explores the T Cell Receptor (TCR) signaling pathway, emphasizing the importance of T cells in the immune system. T cells, differentiated into CD4+ (Helper) and CD8+ (Cytotoxic) subsets, play vital roles in combating infections and tumors. The TCR interacts with antigens presented on MHC molecules, activating T cells and triggering a cascade of cellular responses. We delve into the molecular mechanisms of T cell activation, including the role of kinases, the significance of pMHC agonists, and the implications for organ transplantation and autoimmune diseases.

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Understanding T Cell Receptor Signaling Pathways and Their Role in Immune Response
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  1. Team CDK Daniel Packer Rafael Rodriguez Sahat Yalkabov

  2. TCR Signaling Pathway • TCR (T cell receptor) • Molecule found on T Cells • Response for recognizing antigens on MHC (Major Histocompatibility Complex) • T cell is activated when TCR engages with antigen

  3. T cells • Belong to white blood cells group called lymphocytes • Play central role in immunity • Distinguished from other cells by the presence of TCR on its surface • Named T cells because they mature in thymus

  4. Electron micrograph of T cell

  5. T cell formation

  6. CD8+ and CD4+ T cells • CD8+ (Cytotoxic T cells) • Destroy virally infected cells and tumor cells • Transplant rejection • Recognize targets by binding to antigens associated with MHC class I • Present on ~99.9% of the cells in the body • Deactivated to anergic (inactive) state with the help of molecules secreted by the T-reg cells • To prevent autoimmune diseases

  7. CD8+ and CD4+ T cells • CD4+ (Helper T cells) • Assist white blood cells with immunologic processes, as well as activation of cytotoxic T cells • Activates with peptide antigens from MHC class II molecules (pMHC) • Expressed on the surface of APCs • When activated, divide rapidly and secrete small proteins called cytokines • Regulate or assist active immune response

  8. MHC • Cell surface molecule • Mediate interactions between white blood cells and other immune cells or the body cells • Determines compatibility of organ transplants • Measures the susceptibility to autoimmune diseases • In humans, MHC also called HLA (human leukocyte antigen) • MHC region occurs on chromosome 6

  9. Structure of TCR • Member of immunoglobulin superfamily • Consists of 2 halves: • Alpha/Beta and Gamma/Delta fragments • Structure similar to immunoglobulin Fab fragments

  10. Generation of TCR 1/2 • Alpha/Gamma chain - generated by VJ recombination • Beta/Delta chain – generated by V(D)J recombination • Intersection corresponds to CDR3 region • Important for antigen-MHC recognition

  11. Generation of TCR 2/2 • Involves random joining of gene segments to complete TCR chain • Unique combinations of segments, as well as palindromic and random N- and P- nucleotide additions accounts for great diversity

  12. T cell activation 1/2 • TCR complex identifies specific bound antigen and elicits a distinct response • The mechanism by which T cells evoke response is called T cell activation • The most common mechanism for activation is via phos./dephos. by proten kinases. • TCR associated reactions kinases: • Lck • Fyn • CD45 • Zap70

  13. T cell activation 2/2 • pMHC(agonist) • Interacts even at low concentrations • pMHC(endogenous) • Weak interactions / No effect

  14. Target molecule: ERK • Extracellular signal-regulated kinases • Involved in regulation of meiosis, mitosis, and postmitotic. • Activates on: • Growth factors, cytokines, virus infection, transforming agents, carcinogens.

  15. Results

  16. Results

  17. Results

  18. Results

  19. Results

  20. Results

  21. Conclusion • pMHC(endogenous) had little to no effect on the activation times of ERK • pMHC(agonist) had a very noticeable effect on the activation times of ERK • ERK concentration starts around 202,000 and tops out at 296,000 • The activation times of ERK depend on pMHC(agonist) concentrations • The greater pMHC concentration, quicker are the activation times and smaller the time distribution