Immunology Chapter 5 – Antigen recognition by T lymphocytes
Lines of defense
1. Barriers (chapter 2)
2. Innate immune system (chapter 2/3)
3. Adaptive immune system → in this chapter
a. B-cell
b. T-cell
i. CD4+ T cell: help other immune cells
ii. CD8+ T cell: kill infected cells
How it all starts
T-cells are developed in the Thymus → activation in secondary lymphoid organs
(activation occurs via T-cell receptor (TCR) by recognition of antigen) → cellular
response
Big difference between B- and T-cells
• B cell receptor: recognize intact antigens (proteins, carbohydrates, DNA)
• T cell receptor: recognize process (small) antigen that is presented in MHC by
dendritic cell
T-cell receptor structure
TCR consists of 2 chains:
1. Alfa chain: It resembles Immunoglobulin (B-cell) light
chain
a. Variable region (antigen-binding site): 2 gene
segments
b. Constant region: one gene segment
c. Transmembrane region
2. Beta chain: It resembles Immunoglobulin (B-cell) heavy chain
a. Variable region (antigen binding site): 3 gene segments
b. Constant region: one gene segment
c. Transmembrane region
TCR strongly resembles immunoglobulin Fab fragment, although it is always
membrane bound!
One TCR defines a single T cell clone and only recognizes one specific epitope
The TCR is ONLY equipped for antigen recognition but has no effector functions like
Immunoglobulin!
TCR diversity
Every individual T cell has its own unique TCR (variable domain) - 109 different TCR
How to generate so many TCR (variable domain)? By somatic recombination (gene
rearrangements
, Alpha chain: Germline DNA (cannot be translated into protein) → variable region bind
to joining region by somatic recombination → rearranged DNA → primary RNA by
transcription → mRNA by splicing → polypeptide chain by translation.
Beta chain: Germline DNA (cannot be translated into protein) → diversity segment
bind to joining segment by somatic recombination → variable region bind to diversity-
joining region by somatic recombination → rearranged DNA → primary RNA by
transcription → mRNA by splicing → polypeptide chain by translation.
Total diversity of T-cell = 1*1018 → more diversity than BCR
Recombinase activating genes (RAG)
Somatic recombination is initiated via RAG1 and RAG2.
The somatic recombination starts with the heavy chain
(VDJ) and later it will recombine the light chain.
RAG is only expressed in developing T and B cells in the bone marrow and thymus.
RAG bind to the recognition signal sequence (RSS) next to the VDJ segments
→ they join one sequence with another one (loop) → loop will cut out → 2 regions
next to each other will paced together
People who are RAG deficient don’t have an adaptive immune system – severe
combined immune deficiency (SCID). Need bone marrow transplantation to be able
to survive.
TCR membrane expression
Stable TCR complex consists of:
- TCRalfa and TCRbeta chain: on its own they only recognize the
antigen
- CD3 complex: it has 3 components (epsilon, delta and gamma):
associated with the TCR to make a stable complex. Signalling via
cytoplasmic tail
- Zetta chain (inside the cell). Signalling via cytoplasmic tail
Antigen processing and presentation
Recognition of processed (small) antigen by TCR:
1. Presence of pathogen in a cell
Two origins: extra-or intracellular
2. Pathogen processing for antigen retrieval
through degradation into peptides
Two location in a cell:
• Extracellular pathogen (bacteria)
Lines of defense
1. Barriers (chapter 2)
2. Innate immune system (chapter 2/3)
3. Adaptive immune system → in this chapter
a. B-cell
b. T-cell
i. CD4+ T cell: help other immune cells
ii. CD8+ T cell: kill infected cells
How it all starts
T-cells are developed in the Thymus → activation in secondary lymphoid organs
(activation occurs via T-cell receptor (TCR) by recognition of antigen) → cellular
response
Big difference between B- and T-cells
• B cell receptor: recognize intact antigens (proteins, carbohydrates, DNA)
• T cell receptor: recognize process (small) antigen that is presented in MHC by
dendritic cell
T-cell receptor structure
TCR consists of 2 chains:
1. Alfa chain: It resembles Immunoglobulin (B-cell) light
chain
a. Variable region (antigen-binding site): 2 gene
segments
b. Constant region: one gene segment
c. Transmembrane region
2. Beta chain: It resembles Immunoglobulin (B-cell) heavy chain
a. Variable region (antigen binding site): 3 gene segments
b. Constant region: one gene segment
c. Transmembrane region
TCR strongly resembles immunoglobulin Fab fragment, although it is always
membrane bound!
One TCR defines a single T cell clone and only recognizes one specific epitope
The TCR is ONLY equipped for antigen recognition but has no effector functions like
Immunoglobulin!
TCR diversity
Every individual T cell has its own unique TCR (variable domain) - 109 different TCR
How to generate so many TCR (variable domain)? By somatic recombination (gene
rearrangements
, Alpha chain: Germline DNA (cannot be translated into protein) → variable region bind
to joining region by somatic recombination → rearranged DNA → primary RNA by
transcription → mRNA by splicing → polypeptide chain by translation.
Beta chain: Germline DNA (cannot be translated into protein) → diversity segment
bind to joining segment by somatic recombination → variable region bind to diversity-
joining region by somatic recombination → rearranged DNA → primary RNA by
transcription → mRNA by splicing → polypeptide chain by translation.
Total diversity of T-cell = 1*1018 → more diversity than BCR
Recombinase activating genes (RAG)
Somatic recombination is initiated via RAG1 and RAG2.
The somatic recombination starts with the heavy chain
(VDJ) and later it will recombine the light chain.
RAG is only expressed in developing T and B cells in the bone marrow and thymus.
RAG bind to the recognition signal sequence (RSS) next to the VDJ segments
→ they join one sequence with another one (loop) → loop will cut out → 2 regions
next to each other will paced together
People who are RAG deficient don’t have an adaptive immune system – severe
combined immune deficiency (SCID). Need bone marrow transplantation to be able
to survive.
TCR membrane expression
Stable TCR complex consists of:
- TCRalfa and TCRbeta chain: on its own they only recognize the
antigen
- CD3 complex: it has 3 components (epsilon, delta and gamma):
associated with the TCR to make a stable complex. Signalling via
cytoplasmic tail
- Zetta chain (inside the cell). Signalling via cytoplasmic tail
Antigen processing and presentation
Recognition of processed (small) antigen by TCR:
1. Presence of pathogen in a cell
Two origins: extra-or intracellular
2. Pathogen processing for antigen retrieval
through degradation into peptides
Two location in a cell:
• Extracellular pathogen (bacteria)
