The T Cell Tome Flashcards
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.
