T lymphocytes -Thrush

Question 1

What is needed in order to activate T cells?

Answer 1

signal #1: TCR + antigen binding + self-MHC

signal #2: CD80/86 on APCs bind to CD28 on T cells

Question 2

What is MHC restriction?

Answer 2

in the periphery a T cell will only be activated when it recognizes its antigenic peptide presented with self-MHC.

Question 3

What is the signaling function in the TCR structure? What is this similar to in B cells?

Answer 3

CD3 complex is the signaling function. It is a signaling domain of 5 polypeptides together in order to produce a signaling cascade

it is similar to Ig alpha/Ig beta in B cells

Question 4

What is the structure of the two types of TCRs? What are the traditional T cells?

Answer 4

the TCR is either a heterodimer of alpha/beta or a gamma/delta heterodimer

traditional T cells are the alpha beta T cells and these are divided into CD4+ and CD8 T cells

Question 5

What are the differences between alpha beta and gamma delta T cells?

Answer 5

alpha beta:
large TCR gene diversity
~60% CD4+
~30% CD8+
t need educated
do not recirculate

Question 6

What will happen as a result of the alpha chain rearrangement?

Answer 6

The delta locus will be cut out and the T cells will be prevented from forming a gamma delta TCR. This prevents both alpha and delta from being produced

Question 7

Where are the alpha, beta, gamma and delta loci located on the TCR genes in association with each other?

Answer 7

the delta locus is embedded within the alpha locus

the beta and gamma chains are on the chromosome but are not linked

Question 8

What domains of alpha, gamma, beta, and delta have and which Ig chains are they similar to?

Answer 8

alpha and gamma have a J and V (similar to Ig light chain)

Beta and delta have V, D, and J (similar to Ig heavy chain)

Question 9

Where does TCR rearrangement occur?

Answer 9

In the thymus

Question 10

How does the process of gene rearrangement produce alpha beta and gamma delta T cells?

Answer 10

The process of TCR gene rearrangement is sequential in that the β, γ, and δ chain rearrange simultaneously.
If the γδ genes are successful first, then the T cell will become a γδ T cell.
If, however, the β chain is successful, a β chain polypeptide will be produced and associates with pre-Tα, a “surrogate” alpha chain. These two will go to the surface of the T cell and will trigger rearrangement of the α chain locus. Once this starts, the T cell will loose its δ locus and cannot become a γδ T cell

Question 11

How is allelic exclusion in T cells different from that of B cells?

Answer 11

In T cells, the α locus is not as tightly controlled and therefore, it’s possible that two α chains may be expressed with a given β chain. However, only one of those α chains will be functional so it is considered a “functional allelic exclusion” in T cells.

Question 12

Are TCRs or Igs more diverse? What adds to this diversity? (5)

Answer 12

there is more diversity in TCRs than in Igs

1. combinatorial joining: higher number of J region genes in T cells than in B cells
2. alternative joining of D segments (beta chain): because of different RSSs, D gene segments can join together in TCRs where they cannot in Igs–> increase in the diversity depending on the number of Dbetas.
3. Junctional flexibility: random addition of bases during joining of cut DNA during rearrangement
4. P nucleotides: palindromic bases added due to repair process/enzymes
5. N nucleotides: Tdt is capable on ALL TCRs (vs. only in the IgH region)

Question 13

What is the TCR complex made of?

Answer 13

TCR and CD3 complex (signaling molecule)

CD3=”Invariant chain”

Question 14

What is the structure of CD3?

Answer 14

mostly intracellular with an intramembrane which is negatively charges to interact with the positive charges of TCR

ITAM are the immunoreceptor tyrosine-based activation motifs which are phosphorylated when the Ag binds–> signaling cascade

Question 15

What do CD4 and CD8 do in the T cells?

Answer 15

Interact with the MHC molecules to help hold it together (TCR itself has a lower affinity than Igs) and participate in some signaling

Question 16

What are adhesion molecules of T cells?

Answer 16

The adhesion molecules LFA-1/ICAM-1 and CD2/LFA-3 help hold together the T cell/APC

Question 17

What can be the second signal in T cell activation?

Answer 17

CD 28 interacting with CD 80/86 (B71/B72)

or cytokines
or CTLA-4 binding to B7–> inhibitory signal

Question 18

Describe the process of T cell development

Answer 18

• T cells originate in the bone marrow and move to the thymus for education
• earliest T cells express CD3 and are CD4-/CD8- (double negative)–> can become either alpha beta or gamma delta T cells
• gene rearrangement begins in the thymus–> for alpha beta T cells BEFORE rearrangement, the T cells will become double positives (CD4+CD8+).
• -> these can proliferate, resulting in the same beta chain and a number of alpha chains.
• T cells begin “T cell education” to insure that self-reactive cells are destroyed and that the T cell can interact with self-MHC
• remaining cells become single positive before leaving the thymus (express either CD4 or CD8)

Question 19

When is CD 25 expressed? What is CD 25?

Answer 19

1. Early T cell development (in the thymus)
2. by activated T cells after recognizing their cognate antigen
3. by Tregs

it is an IL-2receptor alpha gene

Question 20

What is positive selection for T cells? negative selection? What cells are important in selection and why?

Answer 20

Positive selection:
select T cells whose receptors can interact with self-MHC
cells binding to self-MHC get a “protective” signal and survive
stops alpha chain rearrangement (allelic exclusion)

Negative selection:
T cells with high affinity for self-MHC alone and T cells reactive to self-peptides die via apoptosis (cells not reacting are selected)

Thymic stromal cells are important in selection because they have high levels of class 1 and 2 MHC–> important in determining if react with self-MHC

Question 21

What is an inhibitory signal #2 for T cells?

Answer 21

CTLA-4 binds B7 sending a suppression signal

Question 22

What do superantigens bind to? What happens when they are bound? What are some common superantigens?

Answer 22

• bind a particular Vbeta family (NOT antigen specific)
• *ONLY class II MHC and CD4+ T cells
• somehow the super antigen glues together T cell and APC to trick it so it thinks it is recognizing the antigen and causes it to make cytokines
• get activation of a large population of T cells–> high levels of cytokine release
• pathology due to increased cytokines (inflammation, systemic causes shock)
• infection will cause T cells to proliferate but then undergo apoptosis

staphylococcal enterotoxins (SEA, SEB), Toxic-shock syndrome toxin (TSST-1), exfoliative-dermatitis toxin, streptococcal pyrogenic exotoxins, etc.

Question 23

What are some characteristics of NK1-T cells? what do they bind to? What is their effector function?

Answer 23

have rearranged TCRs (alpha beta) (unlike NK cells)
bind to CD1 molecules (not classical MHC) and lipids (Ag)
effector function similar to NK cells (cytotoxic)
secrete cytokines to attract Th cells
may function as a rapid response to invader (don’t need Ag processing of Ag)

Question 24

What are the typical Th cells? What processes are they most involved in?

Answer 24

1) Th0 which are precursor T helper cells. Once the naive Th0 cell sees its antigen, it will become Th1 or Th2 (and will inhibit the other from being produced)
2) Th1 cells which are helpful in regulating cell-mediated immunity by causing cytotoxicity and inflammation
3) Th2 cells which produce antibodies

Question 25

What are CD4+CD25+ Treg cells function in ?

Answer 25

regulating the immune response. thought to play a role in suppressing autoimmune disease