MHC and antigen recognition by T cells

• Describe and compare the origin of B and T cells

  B lymphocytes originate and differentiate in the adult bone marrow. They then migrate to lymphoid tissue such as the spleen, but in particular the lymph nodes. Whereas, T lymphocytes originate in the bone marrow and then differentiate to form mature T cells in the thymus. Following this they then migrate in the same manner as B cells.
• Describe the structure of the B cell receptor

  Consists of a Y-shaped receptor that is made from heavy and light chains. The variable region makes up the complementary determining region (CDR) which determines antigen recognition. This receptor is coupled with signal transducing molecules in the plasma membrane, such as Ig-beta and Ig-alpha, which conduct signals into the cell.

  
• Describe the structure of the T cell receptor

  Consists of one alpha and one beta subunit held together by a disulphide bond, with hyper variable regions at the complementary determining regions (CDR). This allows different T cell receptors to have different CDRs and recognise specific antigen epitopes. This receptor is coupled with signal transducing molecules in the plasma membrane; CD3 molecules, which mediate intracellular signalling.

  
• Describe the difference in structure between MHC1 and MHC2

  Consists of an alpha and beta chain:

  • MHC1: three alpha domains and one beta domain
  • Long alpha chain is bound to the membrane and non-covalently linked to 2-beta chain. This is found on most nucleated cells.
  • MHC2: 2 alpha domains and two beta domains
  • Restricted expression, e.g., macrophages and B cells. Both chains have transmembrane and cytoplasmic domains.

  
• Describe how the cleft shape is determined in class 1 and 2 MHC molecules

  Cleft size is determined by:

  • alpha1 and alpha2 in MHC1
  • alpha1 and beta1 in MHC2

  This determines the antigen that can bind to the cleft
• How are antigenic peptides produced?

  Antigenic peptides are produced from proteins by a process called antigen processing to make small fragments. MHC class 1 presents intracellular antigenic peptides, whereas MHC class 2 presents extracellular antigenic peptides.
• Describe the process of MHC class 1 molecules displaying endogenous antigens

  Class 1 MHCs present intracellular antigens, such as viral antigens.

  1. Antigen is degraded by the proteasome in the cytoplasm
  2. The antigen peptides are then transported by TAP to the RER.
  3. The peptides displace p88 from MHC I in the RER
  4. The peptide bound TAP is then exported
• Describe the processing of exogenous antigen to class II MHC

  Class II MHC is involved in presentation of extracellular antigens, such as bacteria and parasite antigens.

  1. The antigen is taken up by endocytosis and the endosome and lysosome fuse.
  2. The enzymes in the endolysosome degrade the antigens
  3. The endolysosome fuses with class II MHCs on the surface of the cell
• Describe the binding of TCR to the MHC

  TCR binds to both the MHC molecule and the antigenic peptide in the MHC cleft. This recognition is mediated by by other membrane receptors, which play important accessory roles strengthening interaction between T-cells and other cells:

  • CD4: recognise antigen combined with class II MHC
  • CD8: recognise antigen combined with class I MHC

  
• Describe the advantages of MHC-associated recognition

  • Extra recognition mechanism for pathogen to try to evade
  • Recognising different parts of pathogen from antibody
  • Some peptides are from functional parts of protein
  • Can detect antigen that is inside cells
  • Less scope for mutations in pathogens to avoid recognition