The T-Cell Antigen Receptor Complex

1. 1
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi
The T-Cell Antigen Receptor Complex
In vitro “clonal selection” means each daughter cell has the same antigen specificity as the parent cell
Most molecules present on the monoclonal T cells will be identical to the polyclonal T cells EXCEPT for
the antigen combining site of the T cell antigen receptor

2. 2
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi
T cell antigen receptor diversity
• Unlike MHC molecules TcR are highly variable in the individual
• Diversity focused on small changes in the charge & shape presented at the end of the T
cell receptor.
• TcR diversity to the peptide antigens that bind to MHC molecules
• Mechanisms of diversity closely related to T cell development
• Random aspects of TcR construction ensures maximum diversity
• Mechanisms of diversity generation similar to immunoglobulin genes
Generation of diversity in the TcR
COMBINATORIAL DIVERSITY
Multiple germline segments
In the human TcR
Variable (V) segments: ~70a, 52b
Diversity (D) segments: 0a, 2b
Joining (J) segments: 61a, 13b
The need to pair a and b chains to form a binding site
doubles the potential for diversity
JUNCTIONAL DIVERSITY
Addition of non-template encoded (N) and palindromic (P) nucleotides at
imprecise joints made between V-D-J elements
SOMATIC MUTATION IS NOT USED TO GENERATE DIVERSITY IN TcR

3. 3
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi
TcR genes segmented into V, (D), J & C elements
(VARIABLE, DIVERSITY, JOINING & CONSTANT)
Closely resemble Ig genes (a~IgL and b~IgH)
This example shows the mouse TcR locus
TcR a gene rearrangement by SOMATIC RECOMBINATION

4. 4
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi
T-cell co-receptor molecules
CD4 and CD8 can increase the sensitivity of T cells to peptide antigen MHC complexes by ~100 fold
CD8 and CD4 contact points on MHC class I and class II
MHC class-I MHC class-II

5. 5
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi

6. 6
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi
The lack of somatic mutation in TcR helps to prevent autoimmunity

7. 7
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi
If TcR did undergo somatic mutation:
TcR interacts with entire top surface of MHC-peptide antigen complex
Somatic mutation in the TcR could mutate amino acids that interact with the MHC molecule
causing a complete loss of peptide-MHC recognition.
If TcR did undergo somatic mutation:
TcR-MHC interaction is one of many between the T cell
and APC.
On-off rate of TcR determines rate of ‘firing’ to give
qualitatively different outcomes.
Must be of relatively low affinity as cells with high affinity
TcR are deleted to prevent self reactivity.
If TcR underwent affinity maturation, they would be
deleted.

8. 8
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi

9. 9
Dr. Riaz Muhammad
Notes: Advanced Immunology
Chapter# 4: The T-Cell Antigen Receptor Complex
Date: 10th
November, 2019
Made by Amjad Khan Afridi
T-cells
Distinct lineage of cells with unknown functions
1-5% of peripheral blood T-cells
In the gut and epidermis of mice, most T-cells express TcR
Ligands of TcR are unknown
Possibly recognise
Antigens without involvement of MHC antigens - CD1
Class IB genes
Summary
• The TcR was discovered using clonotypic antibodies.
• Antibodies and TcR share many similarities, but there are significant differences in
structure and function.
• The structure and organisation of the TcR genes is similar to the Ig genes.
• Somatic recombination in TcR genes is similar to that in Ig genes.
• The molecular mechanisms that account for the diversity of TcR include combinatorial
and junctional diversity.
• TcR do not somatically mutate.
• The highly variable CDR loops map to the distal end of the TcR.
• The most variable part of the TcR interacts with the peptide.
How CD+T cell and CD8+T cell play role in response of cytosolic antigen and endocytically
process antigen.
Explain this question in the context of antigen processing and representation.