T Lymphocyte Biology Flashcards
What is the nature of T cell receptor specificity in the periphery?
They are monospecific to one MHC-peptide ligand, with all receptors being identical
What are the two types of T cell receptors?
Alpha-beta and gamma-delta, although 95% are alpha beta.
What is the significance of the CDR3 to the T cell receptor?
Most hypervariable region of beta chain which determines most TCR diversity.
Where are gamma-delta T cells mostly present and what is their function? What CD receptor do they lack?
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.
What is one major difference between TCR and BCR?
TCR does not undergo somatic hypermutation as a regulatory mechanism.
What enzymes are required for T cell gene rearrangement?
RAG1 and RAG2 (recombination activating gene)
What does allelic exclusion cause in the T cells? What is the exception?
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.
What are zeta and eta chains?
Two parts of the TCR complex which are alternatively spliced from the same RNA transcript. Two of them sit directly under the TCR.
What are the subunits of CD3 and where does it sit?
Sits right next to TCR, has gamma-epsilon on one side and delta-epsilon on the other.
What are the variability of the zeta/eta chains and CD3?
They are invariant
What are the transmembrane charges of CD3 and zeta/eta chains?
negative, to interact with the positively charged TCR transmembrane domains of alpha/beta chains
What are the tails of CD3 and zeta/eta and what do they do? How many are there per receptor?
ITAM - they are tyrosine kinases for signal transduction, 10 per receptor.
What transduces the signal in TCR?
Once TCR has bound MHC + peptide, CD3 + zeta chain is required for signal transduction (via ITAM). They are mutually dependent and transported together
What is the structure and function of CD4?
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.
What is the structure and function of CD8?
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.
Other than the TCR complex and the co-receptors of CD4 or CD8, what two molecules must bind in a Thelper cell for stimulation?
CD28 of T cell must bind B7 of APC.
CD28 is a homodimer. It is also expressed on 50% of CD8+ cells.
What is the function of CTLA-4 / CD152?
It is a homolog of CD28, and inhibits T cell activation following recent activation of CD4 or CD8 T cells.
It also binds B7
What is the function of CD2 and integrins?
Adhesion molecules for adherence to APC or endothelial cells.
Remember, CD2 is constitutively expressed
What is a homing molecule?
Like L-selectin, binds to addressins on endothelium (for HEV migration)
What is Stage 1 of T cell development? What cell type will leave first?
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.
When is the first stage completed?
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+).
What selection takes place during the double positive stage (stage 2)?
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.
What is the AIRE gene?
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.
What do mutations of AIRE cause?
Autoimmune polyglandular syndrome, type (APS1), destruction of multiple endocrine tissues
