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53 Cards in this Set

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T cells: Key points

1) T cells recognize Ag when __________.

2) T cells recognize ______ Ag.

3)TCRs recognize Ag in association with _____.

4)TCRs are restricted to _____-MHC
1)bound to the surface of cell
H-2K and H-2d
two different mouse class I MHC used to to demonstrate the fact that TCRs are restricted to self-MHC
Exception to the rule that TCRs are restricted to self-MHC
Alloreactivity is when TCR recognize foreign MHC. Often times, this is the reason for graft rejection. T-cells recognize foreign MHC as an _________ without a Ag peptide. ~1-10% of T cells can recognize foreign MHC. In this case T cells are not _________. This Alloreactivity may be due to some kind of cross reactivity.
TCR structure

TCR is a Heterodimer with
ab or gd chains. It is very similar to the Fab portion of the B cell Ab.
Disulfide bonds and membrane anchors hold it together. Similar to B cell Ab there is a hInge region, _______ and constant regions, and
three ____(hypervariable regions. CDR3 seems to be the most important in contacting Ag
ab versus gd T cells
-ab are the vast majority of CD3+ cells.
-They have much MORE TCR diversity.
-60% ARE CD4+ compared to <1% in gd
-ab are predominantly CD4+ where as gd are mostly CD8+
-CD4+ are restricted to MHC class II & CD8+ are restricted to MHC class I, where as in gd there are no restrictions.
-ab respond to the MHC-Ag peptide complex, whereas gd mostly just respond to phospholipid Ag
In TCR genes the _____ locus is within the _____ locus, while the ______ and ______ loci are on the same chromosome but seperated.
TCR genes continued

alpha and gamma have a __ and __ (similar to Ig light chain)
beta and delta have a _, _, and _ (similar to Ig H chain)
TCR genes continued

Because the alpha locus is split by delta locus, a
productive rearrangement of ALPHA DELETES THE DELTA LOCUS the purpose of this is?
So that you can’t have both a and d.
Describe the C region of the TCR in relation to the IgH chains. Why are they different.
They are much simpler than IgH chains.
They have no different biological activities of TCRs.
TCR gene rearrangement occurs in the _______
Placement of V & J regions in TCR gene rearrangement is directed by RSS (recombination signal sequences) which consists of a _______-_______-________. Spacer is a _______ sequence.
12 OR 23 BP
In TCR gene rearrangement the ______ genes/enzymes are involved in cutting and pasting the V,D, J regions together
TCR gene rearrangement is a sequential process (as with Ig genes) the beta, gamma, and delta chain ____________.
If gamma delta have complete rearrangement first, then it will be a gamma delta T cell
If beta is first, it associates with a ______ goes to surface, and signals alpha rearrangement to begin.
In doing this, we delete the delta locus. The final result is that the T cell will be an ________.
Allelic exclusion means
for a given T cell, only one allele should be expressed at the same time
Exception for allellic exclusion
alpha locus not as tightly controlled so we CAN SEE 2 ALPHA ON THE SURFACE WITH THE SAME BETA CHAIN.

Most often, one TCR alpha beta is self-MHC restricted (i.e., functional)
Diverisity of TCR - compare it to Ig diversity and explain.
more diversity in TCR than in Ig(even though fewer V region genes) because there is a HIGHER NUMBER OF J REGIONS.
Adding to the diversity of TCR is the fact that we can have alternative joining of ______ regions on the beta chain.
D regions
Diversity of T cells is due to
1) Junctional flexibility

2) P nucleotides
(palindromic base additions)

3) N nucleotides (TDT enzyme addition)

these three thought to generate ~1013 possibilities (~107 for Abs)
T cells are different from B cells in that you get NO SOMATIC HYPERMUTATION. True or False
Explain how diversity in TCR depends on contact with MHC
There are fewer V region genes because have to contact limited number of MHC molecules. Specifically,
CDR1 and CDR2 INTERACT DIRECTLY WITH MHC so they are not very diverse.
There are higher number of J regions because these are the areas that have higher contact with Ag peptides (CDR3).
TCR complex
TCR and CD3 complex
Describe CD3
- intramembrane is NEGATIVELY CHARGED (to interact with positive charges of TCR)
-it has a SIGNALLING FUNCTION which utilizes ITAMs (immunoreceptor tryosine-based activation motifs)
- there are 3 ITAMS in the zeta homodimer and one on other CD3 polypeptides

-When binding Ag, conformational changes send signals to CD3 which then starts signaling cascade.
T cell accessory molecules (co-receptors)
CD4 contacts beta2 domain of class II
CD8 with alpha3 domain of class I
importance of coreceptors
Increase avidity of TCR with MHC and are needed for optimal signaling

100 TCR/Ag/MHC for activating T cell WITH CO-RECEPTOR

10,000 TCR/Ag/MHC for activating T cell WITHOUT CO-RECEPTOR(rarely would happen
Adhesion molecues
help hold T h/T c and Ag presenting cell/ Target cell together
2nd signal in T cells
CD28 cell(on T helpser cell)binds with B7 (on presenting cell)
T cell maturation/differentiation
progenitor T cells originate in bone marrow and move to thymus to be “educated”
lack of thymus showed ________
T cell defects

e.g., DiGeorge Syndrome
T cell maturation/differentiation (cont.)

Earliest T cells express CD2 and are _______ or CD4-/CD8-

These cells go on to become either ab or gd T cells

Gene rearrangement begins in thymus
Describe the Pre-T cell receptor stage of T cell maturation/differentiation
You have CD3, beta chain and pre-Talpha.
There is no CD4/CD8 expressed (double negative)

This stage is important in signaling to continue development (start alpha chain rearrangement)
T cell maturation/differentiation (cont.)

Double negatives become ________(CD4+/CD8+)

These cells proliferate before alpha chain gene rearrangement. This increases diversity by putting same beta chains with different alpha.
T cell maturation/differentiation (cont.)

After successful ab gene rearrangement, cells “tested” for binding
self reactive cells __________ (~98% of all T cells. Surviving cells become __________.
Thymic selection consists of what two selection processes
-positive selection
-negative selection
describe positive selection
select T cells that can interact with self-MHC
describe negative selection
T cells with high affinity for self-MHC alone &
T cells reactive to self-peptides die via apoptosis (cells not reacting are selected)
which cells do the selecting
thymic stromal cells because they have high levels of MHC I & II
How long does the selection process take
~3 weeks
After which stage of selection does cell become CD4+ or CD8+
After negative selection
two-signal hypothesis
In order to be activated, T cells need two signals
What are the 2 signals for T cells
Signal #1: TCR – Ag/MHC
Signal #2: CD28 / B7
What is the significance of CTLA-4
It is a 2nd signal that binds B7 with higher affinity than CD28 (on activated T cells)
It may send “suppression” signal
What happens to T cells without 2 signals?
T cells become anergic or apoptotic
What are superantigens?
They bind to a particular V Beta family and result in activation of a large population of T cells
There is a cytokine release.
Pathology is(inflammation, systemic cause shock)
apoptosis/anergy of stimulated T cells

e.g., are staphylococcal enterotoxins, Toxic-shock syndrome toxin, exfoliative-dermatitis toxin, streptococcal pyrogenic exotoxins, etc.
T cell subsets
ab and gd and NK1-T cells
0.5-10% of all T cells
Do not recirculate
Express limited diversity
NK1-T cells
have rearranged TCRs (ab)
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
ab T cell subsets
CD4 (Th cells and Td cells)
& CD8 (Tc and Ts cells)
precursor helper cell (IL-2, IL-4)
IL-2, IFNg, and TNF-b (CMI)
IL-4, IL-5, IL-6, and IL-10 (Ab)
Delayed type hypersensitive T cells (Tdth)
CD4 cells that stimulate inflammation
CD8 (Tc and Ts cells)
suppressor T cells