Lecture 15

Organized Notes: T Cell Biology

1. T Cell Receptor (TCR) & B Cell Receptor (BCR)

• TCR & BCR Overview (Made on BioRender)

2. T Cell and MHC Interaction

• CDR3 binds to the peptide (most diverse region)

• CDR1 & CDR2 bind to the MHC complex

3. MHC Restriction

• T cells are MHC-restricted (recognize only self-MHC)

• Each T cell recognizes only one antigen (Made on BioRender)

4. T Cell Co-Receptors & Co-Stimulators

• Signal 1: (MHC + peptide) + TCR interaction

• CD3 complex required for TCR signaling

• ITAMs (Immunoreceptor Tyrosine-based Activation Motifs) essential for signaling

5. TCR Signaling Complex

• Signaling occurs via ITAMs

• CD4/CD8 act as co-receptors (stabilize MHC-TCR interaction)

• LcK phosphorylates ITAMs → Initiates signaling (Made on BioRender)

6. TCR Formation & Diversity

• TCR Formation

  • Chromosome 14 & Chromosome 7 (Made on BioRender)

• VDJ Recombination

  • BCR & TCR rearrangement → T cell diversity

7. T Cell Development in the Thymus

• Thymic Involution & Aging

  • Thymus shrinks with age, reducing T cell production (Parham Fig.7.4)

• Stages of T Cell Development

  • Double Negative (DN) Stage

    • DN1: Cells migrate to the thymus

    • DN2: Heavy chain rearrangement

  • Competition: Gamma Delta vs. Alpha Beta T Cells

    • β vs. γδ chain rearrangement determines fate

    • γδ first → γδ T cell; β first → αβ T cell (Made on BioRender)

  • Summary of DN Stage

8. Double Positive (DP) T Cell Stage

• Central Tolerance (Positive & Negative Selection)

  • Positive Selection: Can bind to MHC (occurs in the cortex)

  • Negative Selection: Recognizes self-antigen (occurs in the medulla)

  • "Goldilocks Model": TCR must receive an intermediate signal

9. Autoimmune Regulator (AIRE) & Self-Tolerance

• AIRE promotes expression of tissue-specific antigens in the thymus

• Ensures negative selection against self-reactive T cells

10. CD4 vs. CD8 Lineage Commitment

• CD4+ 8+ (Double Positive) T cells differentiate into either CD4 or CD8

11. Summary of T Cell Development

12. T Cells in the Periphery

• Naïve T cells migrate to secondary lymphoid organs (spleen & lymph nodes)

• T cells become activated upon encountering an antigen