Adaptive Immunity: T-Cell Response I

• What is the precursor for T cells?

  Common lymphoid progenitor (CLP) cells which originate in the bone marrow

  
  

  -and then migrate to the thymus where they maturate

  
• What are the 3 main types of T cells?

  Cytotoxic T cells (CTL)- Vital in controlling intracellular pathogens

  T helper cells

  Regulatory T cells- makes sure that the immune system isn’t over activated
• What do T helper cells do?

  -They regulate the adaptive immune response including activation of immune cells e.g T cells, B cells, Macrophages and dendritic cells

  
  

  -This activation is mediated by cytokines released by Th cells
• What do cytokines do?

  They bind to specific receptors on surface of target cells & initiate cell-signalling (hormone-like)

  
• What are interleukins important for?

  -Type of cytokine

  
  

  -Important for tuning the immune response IL-1 IL-2 IL-3 (in order of discovery)
• What do CTLs (cytotoxic T lymphocyte) do?

  They recognise cells that are infected by intracellular pathogens & induce programmed cell death (apoptosis)
• What are the 3 ways that CTLs can induce apoptosis?

  1. Secretion of TNF (tumour necrosis factor) which binds to TNF receptor

  
  

  2. CTL secretes perforin & granzymes

  
  

  3. Fas ligand (TNF homologue) binds to Fas (TNF receptor homologue)

  
• What do all T cells express?

  A cell surface (membrane bound) antigen receptor (TCR) formed by 2 polypeptides – α chain and β chain

  Unconventional T cells have antigen receptors formed by gamma and delta chains.

  Each T cell has receptor of unique specificity

  
• Does TCR bind to the antigen directly?

  No, it will only bind to fragments of antigens (peptides) that are bound to major histocompatibility complex (MHC) proteins on the surface of the target cell
• What are the 2 types of MHC?

  Class I and Class II

  
  

  MHC class I: overall structure similar but α polypeptide is larger and forms complete peptide binding domain β2microglobulin

  
  

  -(β2m) is not transmembrane domain

  
• What is the structure of MHC II:

  
• What does it look like when a T helper cell binds via TCR to an MHC II complex with a peptide?

  -Alpha helices (shown in red) along with the peptide are recognised by the TCR

  
  

  - So its not just the peptide or just the MHC that it recognises, they are recognised by TCR when together.

  
• What is CD3?


  Complex of 6 transmembrane proteins

  
  

  Forms part of TCR complex and transmits activation signal
• Do CTLs express CD4?


  No, but they express CD8 in association with the T cell receptor

  
• What is CD8?


  A dimer & type of protein on the plasma membrane of T-cells

  
  

  TCR of CTL is associated with CD8 which binds to MHC I

  
• What are the differences between MHC class I & II proteins?

  
• Summarise the content in this lecture.