CMB2004/L03 Genetics of Antigen Recognition Systems II

Question 1

What encodes TCR polypeptides?

Answer 1

Rearranging gene segments
TRA, TRB, TRG, TRD gene loci

Question 2

Where do gene segments rearrange during T cell development?

Answer 2

In the thymus

Question 3

Give 3 mechanisms involved in TCR diversity.

Answer 3

Multiple V (D) & J gene segments
Combinatorial diversity
Junctional diversity

Question 4

Give one key difference between BCR and TCR.

Answer 4

TCR is never secreted
No SHM in TCR genes

Question 5

Describe TCR generation. (3)

Answer 5

Germline DNA recombination
Rearranged DNA transcription, splicing and translation
Protein (T-cell receptor)

Question 6

Where does a T cell break DNA and rejoin?

Answer 6

Broken between D and J
Randomly rejoined

Question 7

Where do TCR recognise Antigens?

Answer 7

In groove of MHC molecules

Question 8

What gene rearrangement occurs in MHC molecules?

Answer 8

None

Question 9

Which chromosome are MHC molecules encoded?

Answer 9

HLA on chromosome 6

Question 10

How many MHC molecules can a single person have?

Answer 10

Up to 12 if heterozygous for all 6 MHC loci (co-dominant expression)

Question 11

Why is location of polymorphic residues within MHC molecules not random?

Answer 11

It affects peptide binding

Question 12

Why are levels of MHC polymorphism so high?

Answer 12

Allows binding of range of peptides presented to T cells

Question 13

Give a downside to highly polymorphic MHC.

Answer 13

Increases risk of immune-mediated diseases
Reduces pool of available donor organs

Question 14

What needs to occur to protein antigens before they can bind and be presented by MHC molecules?

Answer 14

Processing into small peptide fragements

Question 15

Describe the presentation of antigens by MHC class I molecules. (4)

Answer 15

Intracellular antigen processed to peptides in proteasome
Peptide transport into ER by TAP transporter
Peptide binding by MHC class I
MHC class I presents peptide at cell surface

Question 16

What occurs to the proteasome when receiving inflammatory cytokines?

Answer 16

Modified to produce altered peptides

Question 17

Describe the role of TAP. (2)

Answer 17

Component of multi-protein assembly - peptide loading complex
Includes tapasin and calreticulin
Delivers peptides to MHC class I molecules

Question 18

Describe binding and presentation of antigens by MHC class II molecules. (3)

Answer 18

Extracellular antigen degraded to peptides by acid proteases in phagolysosome
Peptide binding by MHC class II
MHC class II presents peptide at cell surface

Question 19

Explain the role of the invariant chain and HLA-DM in MHC class molecule binding. (5)

Answer 19

Invariant chain forms complex with MHC class II blocking binding
Ii cleaved in acidified endosome; short peptide fragment (CLIP) still bound to MHC class II
Endocytosed antigens degraded to peptides but CLIP blocks binding to MHC class II
HLA-DM binds to MHC class II to release CLIP and allows other peptides to bind
MHC class II travels to cell surface

Question 20

In normal healthy cells, what other antigen sources with MHC class I and II molecules present?

Answer 20

Self proteins

Question 21

Where are accessory molecules to antigen processing encoded?

Answer 21

Within the MHC gene
TAP and LMP (class I)
HLA-DM (class II)

Question 22

Which cells recognise and kill cells infected with MHC class I-presented antigens

Answer 22

Cytotoxic CD8+ cells

Question 23

Give another name for cells expressing MHC class II molecules.

Answer 23

Antigen-presenting cells

Question 24

Which cells are activated by APC/MHC class II molecules?

Answer 24

Helper CD4+ cells