T cell development, Generation of receptor repertoire diversity Flashcards
1
Q
What are the main events in lymphocyte development
A
- Commitment
- Proliferation
- Selection
- Differentiation into distinct functional effector subpopulations
2
Q
What cell lineage gives rise to B and T cells
A
Haematopoetic stem cells
3
Q
What are the stages of T cell development
A
- Stem cell
- Pro-lymphocyte
- Pre-lymphocyte
- Immature lymphocyte
- Mature lymphocyte
4
Q
Describe the anatomy of the thymus gland
A
- Gland located above the heart
- Lobular organ
- Comprised of a cortex and a medulla
- Has a dense network of stromal cells and lymphocytes
5
Q
Describe the journey of T cells through their development
A
- Common lymphoid progenitor becomes Pro-T with the help of Notch signals by thyme storm and Induction of GATA3
- Intense proliferation in the thymus
6
Q
How can T cell lineages be identified
A
- Receptor identification by flow cytometry
- Split into 4 quadrants comparing CD8 and CD4 receptor expression
7
Q
Describe the structure of a T-cell receptor
A
- Heterodimer consisting 3 transmembrane polypeptide chains linked by disulphide bridges
- 2 types - alpha beta, gamma delta
8
Q
What structures are present to aid the function of the TCR
A
- The C regions have cysteine residues that bring the chains together
- Charged residues in the transmembrane region bind to CD3 and the zeta chain to form the TCR signalling complex
- CD3 and zeta allow for the transduction of signals upon MHC-peptide binding
9
Q
Explain how TCR binds to MHC
A
- Peptides bind to MHC receptors
- T cells recognise linear peptides and are not conformational determinants of protein antigens
- T cells recognise cell associates and not soluble antigens
- CD4 and CD8 cells recognise different classes of MHC
10
Q
What is MHC (major histocompatibility complex)
A
- MHC class I molecules present peptide antigens derived from pathogens that replicate inside the cell, such as viruses.
- MHC class II molecules present peptides from pathogens and antigens that are present outside the cell taken up by endocytic vesicles of phagocytic cells.
11
Q
Describe the structure of MHC receptor
A
- Extracellular peptide binding cleft
- Ig-like domain
- Cytoplasmic tail
- MHC class II has a conserved CD4 binding site
- MHC class I has a conserved CD8 binding site
12
Q
How do MHC molecules achieve very high polymorphic and polygenic rates
A
- There are multiple variants of each gene within the population
- Contains several different MHC class I and class II genes. Thus every individual possesses a set of MHC molecules with different ranges of peptide binding specificities
13
Q
How does the polymorphic residue location affect MHC-peptide interactions
A
- Each MHC has one cleft that binds one peptide at the
time but can bind different peptides - Peptides that bind one MHC share structural features
that promote binding - Minimal number of MHC-peptide complexes can
activate a T cell - MHC molecules can bind and display foreign and self
peptide - MHC class II binds to longer peptides than class I
14
Q
What cells express MHC class 1 and 2
A
- MHC class I. All cells but erythrocytes
- MHC class II. Antigen presenting cells
15
Q
Describe the process by which peptides are presented on MHC II
A
- Uptake of extracellular proteins into vesicular compartments
- Process of internalised proteins in endosome
- Biosynthesis and transport of MHC II molecules to endosome
- Peptide association with MHC II
- Expression of peptide-MHC complex on cell surface
