T Lymphocyte Biology

Question 1

What is the nature of T cell receptor specificity in the periphery?

Answer 1

They are monospecific to one MHC-peptide ligand, with all receptors being identical

Question 2

What are the two types of T cell receptors?

Answer 2

Alpha-beta and gamma-delta, although 95% are alpha beta.

Question 3

What is the significance of the CDR3 to the T cell receptor?

Answer 3

Most hypervariable region of beta chain which determines most TCR diversity.

Question 4

Where are gamma-delta T cells mostly present and what is their function? What CD receptor do they lack?

Answer 4

Mostly present in lung, skin, and intestine vs the blood. Unique in that they can respond to phospholipids as well as peptides. They are a first line of defense.

They lack CD4 receptors, although they still express CD3.

Question 5

What is one major difference between TCR and BCR?

Answer 5

TCR does not undergo somatic hypermutation as a regulatory mechanism.

Question 6

What enzymes are required for T cell gene rearrangement?

Answer 6

RAG1 and RAG2 (recombination activating gene)

Question 7

What does allelic exclusion cause in the T cells? What is the exception?

Answer 7

inhibits the rearrangement of the second TCR beta gene on the other chromosome once TCRbeta has successfully rearranged.

Does not block alpha rearrangement, thus it is possible to have two different alpha chains on one T cell.

Question 8

What are zeta and eta chains?

Answer 8

Two parts of the TCR complex which are alternatively spliced from the same RNA transcript. Two of them sit directly under the TCR.

Question 9

What are the subunits of CD3 and where does it sit?

Answer 9

Sits right next to TCR, has gamma-epsilon on one side and delta-epsilon on the other.

Question 10

What are the variability of the zeta/eta chains and CD3?

Answer 10

They are invariant

Question 11

What are the transmembrane charges of CD3 and zeta/eta chains?

Answer 11

negative, to interact with the positively charged TCR transmembrane domains of alpha/beta chains

Question 12

What are the tails of CD3 and zeta/eta and what do they do? How many are there per receptor?

Answer 12

ITAM - they are tyrosine kinases for signal transduction, 10 per receptor.

Question 13

What transduces the signal in TCR?

Answer 13

Once TCR has bound MHC + peptide, CD3 + zeta chain is required for signal transduction (via ITAM). They are mutually dependent and transported together

Question 14

What is the structure and function of CD4?

Answer 14

It is a monomer with 4 extracellular domains. Serves as a co-receptor, which enhances the binding of alpha-beta TCR to MHC Class 2 by bringing the tyrosine kinase adaptor molecules closer to TCR for signal transduction.

Question 15

What is the structure and function of CD8?

Answer 15

Also a co-receptor which increases binding 100-fold of MHC Class 1. It has a long tail, and is a heterodimer with alpha and beta domains.

Question 16

Other than the TCR complex and the co-receptors of CD4 or CD8, what two molecules must bind in a Thelper cell for stimulation?

Answer 16

CD28 of T cell must bind B7 of APC.

CD28 is a homodimer. It is also expressed on 50% of CD8+ cells.

Question 17

What is the function of CTLA-4 / CD152?

Answer 17

It is a homolog of CD28, and inhibits T cell activation following recent activation of CD4 or CD8 T cells.

It also binds B7

Question 18

What is the function of CD2 and integrins?

Answer 18

Adhesion molecules for adherence to APC or endothelial cells.

Remember, CD2 is constitutively expressed

Question 19

What is a homing molecule?

Answer 19

Like L-selectin, binds to addressins on endothelium (for HEV migration)

Question 20

What is Stage 1 of T cell development? What cell type will leave first?

Answer 20

Bone marrow cells arrive at the thymus as double negative (CD4-CD8-). They rapidly proliferate and expand, commiting to T cell lineage.

Gamma-delta T cells will leave first.

Question 21

When is the first stage completed?

Answer 21

After the TCR properly displays alpha chain following process of gene rearrangement of beta chain including allelic exclusion.

When it leaves, the cell will be double positive (CD4+CD8+).

Question 22

What selection takes place during the double positive stage (stage 2)?

Answer 22

Positive selection - T cells bind with weak affinity to self MHC
Negative selection - T cell binding is too strong - recognition of self = apoptosis
Death by neglect - unreactive T cells to MHC die via apoptosis after neglect.

Question 23

What is the AIRE gene?

Answer 23

AutoImmune REgulator gene

Codes for a transcription factor which promotes the expression of tissue-specific antigens in thymic medullary cells to check for self reaction. We don’t know how developing T cells see all of the antigens in the body.

Question 24

What do mutations of AIRE cause?

Answer 24

Autoimmune polyglandular syndrome, type (APS1), destruction of multiple endocrine tissues

Question 25

How do T cells become single positive?

Answer 25

Double positive thymocytes which bind MHC 1 become CD8 only.

Double positive thymocytes which bind MHC 2 become CD4 only.

Question 26

What will absence of MHC Class 2 on thymic epithelial cells cause?

Answer 26

Development of only CD8+ cells, no CD4+ cells.