Generation Of Diversity In The T-Cell Repitoire

Question 1

when can the TCR bind to antigenic peptides?

Answer 1

only when the peptides are in complex with MHC molecules on APC’s

Question 2

Which immune cells recognise and process antigen?

Answer 2

APC’s!!!!

monocytes
macrophages (terminally differentiated monocytes)
dendritic cells
B cells

Question 3

macrophages vs dendritic cells?

Answer 3

both rare in peripheral blood - enriched in mucosal tissues

highly phagocytic cells – induce strong T-cell responses and inflammation. Important for protection against Mycobacterium tuberculosis

Macrophages better-equipped to kill pathogens (higher NO production)

DCs better at migrating to lymph nodes (via CCR7) and presenting antigen to T- cells

Question 4

what 2 things are involved in the commitment of t cells and the process

Answer 4

Notch 1 and Gata3

Notch signals by the thymic stroma
Induction of GATA3
Commitment to the T cell lineage
Intense proliferation

Question 5

successive stages in T cell development are marked by changes in the surface receptors

Answer 5

Successive stages in T cell development are
marked by changes in surface receptors
• 1 week after arrival of precursors into the thymus progenitors commit to the T cell lineage
• Express early markers of the T cell lineage (CD2 and Thy 1)
• Do not express any of the markers that define T cells later in development or after in the periphery (CD3, CD4, CD8)
• Because of the absence of CD4 and CD8 early developing T cells are called DN (double negatives)
• At DN stage developing T cells (thymocytes) re-arrange the TCR locus
• Stages post DN are characterized by the expression of both CD4 and CD8 and later just one or the other

Question 6

the t cell receptor

Answer 6

Upon successful rearrangement and in the periphery (if selected) T cells express high levels of TCR chain
TCR is a heterodimer consisting of two transmembrane polypeptide chains covalently linked to each other by
disulphide bonds
Two types alpha-beta and gamma-delta
Each chain has one lg-like N terminal variable domain (V) and one Ig-like constant domain (C), a hydrophobic transmembrane region and a short signalling cytoplasmic region
The V regions of both chains contain short stretches of amino acid sequence that is highly variable between receptors. These regions form the CDRs or complementary determining regions. The 3 CDRs of the alpha chain and 3 of the beta chain form
the peptide-MHC binding site

Question 7

which segments does the beta chain consist of

Answer 7

v,d and j

Question 8

which segments does the alpha chain consist of

Answer 8

v and j

Question 9

is the TCR alone in function

Answer 9

NO

Question 10

what else works with the TCR

Answer 10

The C regions have cysteines residues that bring the chains together
Charged residues in the transmembrane region bind to CD3 and the zeta chain to form the TCR signalling complex
CD3 and zeta allow for the transduction of signals upon MHC-peptide binding

Question 11

features of antigens recognised by T cells

Answer 11

• Most t cells recognise peptides and no other molecules
• t cells recognise linear peptides and not conformational determinants of protein antigen
• t cell recognise cell- associated and not soluble antigen
• CD4+ and CD8+ T cells preferentially recognise antigen sampled from the extracellular and cytosolic pools respectively.

Question 12

what does MHC stand for

Answer 12

Major histocompatibility complex

Question 13

what does HLA stand for

Answer 13

Human leukocyte antigen

Question 14

MHC 1 class presents peptides from where

Answer 14

present peptide antigens derived from pathogens that replicate inside cells such as viruses

Question 15

MHC II class present peptides from where

Answer 15

present peptides from pathogens and antigens that are present outside the cell taken up by endocytosis vesicles of pahgocytic cells

Question 16

MHC I encodes for which HLA

Answer 16

HLA- A
HLA-B
HLA-C

Question 17

MHC II encodes for which HLA

Answer 17

HLA-DP
HLA-DQ
HLA-DR

Question 18

structure of MHC II

Answer 18

• Extracellular peptide binding cleft 
• Ig-like domain 
• Cytoplasmic tail 
• MHC class Il has a conserved 
CD4 binding site 
• MHC class I has a conserved 
CD8 binding site

Question 19

what does it mean when MHC is polymorphic

Answer 19

there are multiple variants of each gene within the population

Question 20

what does it mean when MHC is polygenic

Answer 20

It contains several different MHC class I and class Il genes. Thus every individual possesses a set of MHC molecules with different ranges of 
peptide binding specificities

Question 21

Polymorphic residue location and MHC-peptide

interactions

Answer 21

• Each MHC has one cleft that binds one peptide at the time but can bind different peptides
• Peptides that bind one MHC share structural features
that promote binding
• Acquire peptides while assembled inside the cell
• Peptide-MHC interactions are storable with low off
rate
• Very small number of MHC-peptide complexes can
activate a T cell
• MHC molecules can bind and display foreign and self
peptide
• MHC class Il bids to longer peptides than class I

Question 22

which cells are MHC I expressed on

Answer 22

all cells but erythrocyte

Question 23

which cells are MHC II expressed on

Answer 23

antigen presenting cells

Question 24

CD4+ cells

Answer 24

helper T cells
secrete cytokines
can only see antigen on MHCII

Question 25

CD8+ cells

Answer 25

cytotoxic T cells
Kills cells
can only see antigen on MHC I

Question 26

Pathway of antigen processing and 
presentation on top of MHC class Il

Answer 26

• uptake of extracellular proteins into vesicular compartments of APC
• processing of internalised proteins in endosomal/ lysosomal vesicles
• biosynthesis and transport of class II MHC molecules to endosomes
• Association of processed peptides with class II MHC molecules in vesicles
• expression of peptides -MHC complexes on cell surface

Question 27

Properties of the TCR

Answer 27

• Only one form of TCR is expressed on each T cell.
• This means that each T cell and its daughter cells have only one TCR and one specificity for antigen
• This is a T cell clone
• However, there are an infinite number of different versions of the TCR each with a unique antigen binding site.
• A TCR has only one antigen binding site.
• A TCR is never secreted.

Question 28

which 2 enzymes rearrange the segments

Answer 28

Rag 1 and Rag 2

Question 29

TCR alpha chain genes

Answer 29

They do not have D gene segments
They are rearranged only after the TCRß chain gene locus has been rearranged.
Successive rearrangements may be attempted until a productive rearrangement has been achieved

Question 30

junctional diversity

Answer 30

During the joining of different gene segments, addition (or removal) of nucleotides may create new sequences at junctions.
Mediated by TdT terminal deoxynucleotidyl transferase

Question 31

where does the 2 check point occur during T cell development

Answer 31

• check point for pre-TCR occurs after rearrangement of beta chain
• check point for TCR occurs after rearrangement of alpha genes

Question 32

Allelic exclusion

Answer 32

Signalling through the pre-TCR suppresses expression of the RAG genes.
So, no more rearrangement at this stage, this is allelic
exclusion.
Allelic exclusion ensures that only one TCRß chain gene is expressed.
These events together are known as ß-selection