T-Cell Development and Lineage Commitment

Question 1

Identify where T cells come from

Answer 1

heamatopoietic stem cells -> lymphoid precursor (common lymphoid progenitor

• commitment into t-cells

bone marrow => foetal liver => thymus migration => lymphoid organs [antigen independant]
- early differentiation

• forming distinct effector populations [graduated from t-cell maturation]
• ILC (innate lymphoid cells) differentiate from Pro-T and accumulate in tissues

Question 2

Describe the main steps and processes T cells follow to become mature naive cells

Question 3

Name a few important
- cell surface receptors,
- transcription factors, and
- soluble cytokines
that mediate the early steps of T cell development

Answer 3

=> stem cell differentiation and commitment: c-kit,
notch-1, GATA3 [from common lymphoid progenitor = tissue specific signalling in thymus stroll cells

🔑 cytokines: IL-7, IL-3

Question 4

Identify the regions of the thymus where T cell development occurs as well as the structural cells involved in the process

Answer 4

1. stem cell
   - commitment
   - proliferation
   - initiation
   - growth factor mediated development
2. pro-lymphocyte
   - pre antigen expression [no self]
3. pre-lymphocyte
4. immature lymphocyte
   [development of self antigen]
5. mature lymphocyte [peripheral lymphoid organs]

Question 5

Describe the structure of the T cell receptor

Answer 5

• TCR [MHC restricted]
• heterodimer
• 2 hydrophobic transmembrane regions
• ɑ and β / 𝛾δ
• covalent linkage with di-sulfide bridge
• Ig similar variable region
• constant region
• contains highly variable short amino acid sequences => CDR [complementary determinant regions]
  ɑ chain contains x3 CDR => involved in peptide-MHC recognition

Question 6

Describe the structure of the MHC class II

Question 7

Understand the consequences of the structural relationship between the TCR and the MHC

Answer 7

• MHC contains anchor proteins which help with MHC/TCR binding

Question 8

Describe the genetic processes that produce the TCR

Answer 8

gene rearrangement
- β-selection
- allelic exclusion = only one allele of β. chain can be expressed
- pre-tɑ chain prevents XS rearrangement so β chain can invest sufficient energy to rearrange correctly
- translocation of signalling = ⬆️ of transcription factors
- CHROMOSOME 7: β , 𝛾
- CHROMOSOME 14 : ɑ , δ
- D+J = D-J
- D-J + V = V-D-J [rearranged product]
- V-D-J + C = L-V-D-J
L = leader sequence = determines destination of polypeptide
mRNA => RNA => amino acid => polypeptide chain

Question 9

Identify the stages of early T cell development where TCR rearrangements take place

Answer 9

cortical-medullary junction

Question 10

Understand the concept of allelic exclusion