lecture 18/19 - t cell receptors

Question 1

What are the two classes of T cell receptors?

Answer 1

Alpha beta and gamma delta

Question 2

Compare and contrast early thymocyte types, TCR-gamma-delta and TCR-alpha-beta

Answer 2

Gd is more common in fetal development, no CD4 or 8 coreceptor expression
Not MHC restricted
Ab is more common
TCRs behave like PRRs and bind different ligands
Express CD8 alpha-alpha  plus
Most abundant in gut epithelial tissue
Thymocytes can express either
Both express CD3

Question 3

Compare and contrast gamma-delta and alpha-beta T cells

Answer 3

gamma delta are found in fetal development
receptors: developed in the thymus only express CD3, not CD4 or CD8
not MHC restricted more like PRRs and bind ligands (phospholipids and intact proteins)
express an one unconventional CD8-alpha-alpha+ found in gut epithelial tissues

alpha beta are more commonly developed, assisting in T cell interactions with pAPC
has CD3 portions (epsilon, gamma and delta) and a zeta chain

Question 4

What is the role of CD3 in relation to TCRs?

Answer 4

Needed for TCR assembly, expression and stability

Required for TCR signalling with the zeta chain

Question 5

What controls TCR expression? Is there an exception to this rule?

Answer 5

Allelic exclusion and production nd screening of functional rearrangement

Question 6

Describe the process of ‘TCR gene rearrangement, what enzymes are important and what step are they needed for?

Answer 6

C gamma is deleted upon V alpha and J alpha rearrangement
RAG1 and 2 are crucial for rearrangement
Process is similar to BCR genes

Question 7

What is the function of recombination signal sequences?

Answer 7

Consensus sequences recognized by RAG

Question 8

What is a CDR? At what step would increased diversity be important?

Answer 8

Complementarity determining regions that bind exposed regions if MHC and peptides
CDR3 and 1 interact with the peptide
CRD2 and 1 interact with regions of MHC
During gene rearrangements

Question 9

How would a rescue of a non productive TCR beta chain gene rearrangement be done? What about an alpha chain?

Answer 9

By subsequent rearrangement in the adjacent locus involving another beta rearranging to a DJ beta segment and deleting the unproductive one
for alpha, successive rearrangements until a successful one occurs

Question 10

What is the role of the thymus in the immune response, how does aging impact this organ?

Answer 10

Maturation of bone marrow derived progenitor T cells

Shrinks with age ie less production of naive T cells

Question 11

Describe thymocyte development

Answer 11

Notch receptor needed for signalling, committing thymocytes entering thymus to the T cell lineage
Positive selection → MHC restriction to become SP
Most cells die by neglect before negative selection → removal of autoreactive cells before leaving the thymus

Question 12

What is a double negative thymocyte? Describe the process of getting from DN1-DN4, what is the product?

Answer 12

They undergo Beta selection resulting in proliferation/differentiation
DN1 germline configuration → maturing CD48 thymocyte → , allow for formation fo a pre TCR CD3 complex and early signalling
DN2 dbeta-jbeta rearrangement or alpha gamma chain → CD25 CD44 thymocyte rearranging beta chain genes
DN3 Vbeta-Dveta rearrangement in frame, beta chain protein produced → CD25 CD44 thymocyte cytoplasmic beta
DN4

Question 13

What are DPs and SPs and how do they relate to each other?

Answer 13

Functional TCR alpha chain replaces surrogate
Cell expresses both CD4 and CD8 (double positive
Positive selection → mature single positive (only expressing one)
Surface expression of beta chaon with surrogate, beta rearrangement stops and cell proliferates CD4/8 induction alpha transcription starts → VJ alpha rearrangement alpha:beta:CD3 selection begins→ SP
DP commit to other types of lymphocytes that share properties of both T cells and natural killer cells, some exprews 4 or 8 individually

Question 14

How do NKT cells relate to thymocyte lineage commitment?

Answer 14

Express a TCR w an invariant TCRalpha chain, beta is the normal
Interact with non-polymorphic CD1 molecules presenting lipid antigens
Result in auro immune diseases and cancers

Question 15

What are the 3 possible outcomes of positive and negative selection?

Answer 15

Can’t bind → die by neglect
To strong → negetive selection ie deletion occurs
Just right → positive selection to single positive stage, via selection of thymocytes with appropriate interactions

Question 16

What is an AIRE protein? What happens if this is defective?

Answer 16

Autoimmune regulator protein
Induces expression of many tissue specific proteins for negative selection in medullary
If defective → immune destruction of multiple endocrine tissues → APCECED