4.13 Adaptive immunity T cells Flashcards
What is the structure of the T cell receptor?
How is diversity generated in the T cell receptor?
- Encoded by rearranging TCRa and TCRb genes (similar to Ig)
- TCRa: V, J and C region gene segments
- TCRb V(20), D, J and C region gene segments
- Only one TCR specificity per T cell (allelic exclusion)
Where do mature lymphocytes go to?
- Mature lymphocytes with functional antigen receptor enter the blood circulation and distribute to secondary lymphoid organs
What do T cell receptors recognise?
- TCR recognise pathogen peptides displayed on the cell surface in MHC molecules
- Proteins present in the cytosol, or in vesicles are catabolised to small peptides
- These become complexed with carrier molecules (MHC molecules) and are transported to the cell surface
- Any pathogen the cell is infected with or engulfs also provides peptides to be carried to the surface by MHC molecules.
What are the two types of MHC molecules?
What is the pattern of inheritance for MHC?
- HLA gene products are co-dominantly expressed
- There are hundreds of different MHC (HLA) alleles in the human population - gene polymorphism
- These alleles are not generated by gene rearrangements, as for TCR and BCR, but inherited
- A particular allele can bind a restricted range of diverse peptides.
- Individuals with different alleles bind a different but still diverse range of peptides
Where is the peptide bound to on the MHC?
- Peptide is embedded in MHC binding cleft
- held in place by specific anchor residues
How do peptides get into the MHC? 2 pathways
- Protein antigens may be processed (degraded into peptides) either in endosomes or in the cytosol
- Endosomal processing results in “presentation” on Class II MHC molecules
- Cytosolic processing results in “presentation” on Class I MHC molecules
What is the endogenous antigen pathway for antigen presentation?
What is the exogenous pathway for antigens to be presented?
What are the two major groups of T lymphocytes?
What are the co-receptors for antigen presenting to T cells?
- uses variable domains of the antigen binding sites to peptide and MHC II
- CD4 CD8 coreceptor for that molecule
- To activate either one need antigen presenting cell
What are the three signals for effective activation of naive T cells?
- Antigen presenting cell must acquire and process antigen in compartments which gain access to MHC Class I and Class II pathways
- Interact with naïve T cells to induce effector T cells
- Locate appropriate T cells (in the 20 lymphoid tissue)
- Adhere to T cells
- Present MHC associated peptides to T cells (Signal 1)
- and, importantly provide 2 extra signals
- Provide “co-stimulation” (Signal 2) for T cell expansion
- Induce T cell differentiation (Signal 3)
How do dendritic cells function as antigen presenting cells?
- Many reside in peripheral tissues (skin, gut, lung)
- Highly phagocytic, take up antigen, display peptides on MHC molecules
- APCs become activated by binding PAMPs
- Migrate to the draining lymph node
- Presentation of antigen to T cells
Which co-stimulators are needed in activating naive T cells?
