The T Cell Tome Flashcards
(36 cards)
Describe in brief the TcRs of the immune system.
alpha/beta = heterodimer. alpha is light and beta is heavy chain.
gamma/delta = heterodimer. gamma is light and delta is heavy
Both have Variable, Constant, Transmembrane, and Cytoplasmic regions
Describe the differences between alpha/beta vs. gamma/delta MHC-TcR binding.
alpha/beta can only bind to MHC or CD1d
gamma/delta can bind to non-classical MHC I, stress proteins, heat shock proteins, and do not require MHC presentation of peptides though some do recognize it.
Describe in brief the basic Ig gene structure and how it works.
Variable, Diversity, Joining, and Constant regions.
Ig genes use groups of gene parts to create different possible protein recombinations using recombination dependent RAG1/RAG2 enzymes.
Like dealing out cards after shuffling.
What is essential for TcR diversity?
VDJ rearrangement.
Which VDJ segments are involved in the…
alpha chain of TcRs?
beta chain of TcRs?
V and J
V, D, and J
What are TcR CDR regions?
What is their function?
Complementarity determining regions. They are a part of the variable chains in TcRs.
They are the portion to touch the MHC complex and recognize it.
How does the TcR/MHC interaction influence what is recognized by the TcR?
The MHC/peptide topography must be specific so that the TcR can recognize it. Goldilocks.
If the peptide does not stick out far enough into the TcR or sticks out too far the TcR cannot recognize it well and makes very few clonal expansions.
if the peptide is featured then it can react with many TcRs and clonal expansions will be plentiful.
Briefly explain the TcR bias.
There are 3 types where TcRs will respond based on certain characteristics they possess.
Type 1: Largest group = cells all have same variable regions and differ in CDR3/J regions
Type 2: Medium group = cells all have same variable regions and a conserved motif in CDR3 region
Type 3: Small group - cells use same alpha/beta chain or both.
Describe the scope of alpha/beta T cells and their functions.
CD4+: helper cells. MHC II recognition. Immunomodulatory.
CD8+: cytotoxic cells. MHI I recognition.
NKT cells: CD1d lipid recognition. LImited variable and J region usage.
Describe the scope of gamma/delta T cells and their functions.
They are intraepithelial lymphocytes (IELs) which express gamma/delta TcR. Cytotoxic cell function AND immunomodulatory function.
Where does very early thymocyte development occur?
Further T cell development occurs where? What are the steps (brief)?
Bone marrow.
Migrate to thymus, DN, DP, positive/negative selection, removal of autoreactive cells, release into bloodstream.
When does the a/b or g/d T cell differentiation occur in T cell development? How does this often work? Is there a time when this is different?
There is recombination during the DN stages.
TcRbeta rearrangements are one of the first to take place and most likely to be productive so alpha/beta outcomes are more likely EXCEPT in fetal development.
During DN T cell beta selection, how does this process take place?
there is proliferation and differentiation and only one b chain is rearranged beause of allelic exclusion. The successful beta chain is paired with a pre-Talpha chain.
After beta selection has occurred, T cells are at the ___ stage.
What happens now?
DP stage
Functional TcRalpha chain replaces preTcR alpha chain, cell is still DP, positive and negative selection occurs yielding SP T cell.
Describe the affinity model for T cell selection
It is based on the strength of interaction between TcR and self-MHC complexes. No affinity = death by neglect Little affinity = naive T cell Mid range = Treg Too high = Negative selection.
How many T cells survive selection?
Describe positive selection factors.
Describe negative selection factors/functions.
Fewer than 5%
T cell survival, MHC restriction, SP cell. 90-95% fail positive selection
Clonal deletion: limit recognition of self, self-tolerance. Less than 5% of T cells undergo clonal deletion
Where does T cell +/- selection occur?
Describe these functions.
In discrete thymic microenvironments.
Cortex/medulla provide these to coordinate a spatial and temporal segregation for selection. + selection of mainstream a/b T cells contingent on permissive interactions with APC type cTEC.
On what is positive alpha/beta T cell selection contingent?
Interactions with cortical thymic epithelial cells - cTEC
Why is positive selection crucially dependent on a single stromal cell type when tolerance can be mediated by a variety of cell types?
Likely that proteolytic pathways endow cTECs with largely unique peptide, the MHC ligandome, that is distinct from other things displayed elsewhere.
What is the difference between public/private peptides?
Private peptides are expressed only by cTECs.
Public peptides are expressed by many types of APCs
What is the function of negative T cell selection?
How does this occur?
Describe the other mechanisms postulated.
Ensures self-tolerance.
Clonal deletion remains the best proven and most common method of tolerance induction.
Clonal arrest - auto reactive T cells prevented from maturing
Clonal anergy - inactivation of auto reactive T cells
Clonal editing - 2nd/3rd chance to rearrange non-self reactive TcR alpha gene
How does the medulla function in T cell tolerance?
Tissue restricted antigens by mTECs and unique ensemble of APCs like AIRE allow T cells to be screened safely in the thymus
Describe the three potential ways that the mTECs give T cells the tissue restricted Ags.
Directly - mTEC connects with T cell for TRA transfer
Handover and indirect - mTEC gives Ag to DCs in medulla to interact with T cells
Mosiac - both of the first in many different patches all over the medulla
How is the expression of CD5 relevant for T cells?
Expression on SP T cells is thought to reflect signalling intensity of positively selecting TcR-MHC interaction and CD5 persists on mature T cells.
In infections, CD5hi cells outcompeted CD5low cells for response to pathogens.
