CMB2004/L03 Genetics of Antigen Recognition Systems II Flashcards
What encodes TCR polypeptides?
Rearranging gene segments
TRA, TRB, TRG, TRD gene loci
Where do gene segments rearrange during T cell development?
In the thymus
Give 3 mechanisms involved in TCR diversity.
Multiple V (D) & J gene segments
Combinatorial diversity
Junctional diversity
Give one key difference between BCR and TCR.
TCR is never secreted
No SHM in TCR genes
Describe TCR generation. (3)
Germline DNA recombination
Rearranged DNA transcription, splicing and translation
Protein (T-cell receptor)
Where does a T cell break DNA and rejoin?
Broken between D and J
Randomly rejoined
Where do TCR recognise Antigens?
In groove of MHC molecules
What gene rearrangement occurs in MHC molecules?
None
Which chromosome are MHC molecules encoded?
HLA on chromosome 6
How many MHC molecules can a single person have?
Up to 12 if heterozygous for all 6 MHC loci (co-dominant expression)
Why is location of polymorphic residues within MHC molecules not random?
It affects peptide binding
Why are levels of MHC polymorphism so high?
Allows binding of range of peptides presented to T cells
Give a downside to highly polymorphic MHC.
Increases risk of immune-mediated diseases
Reduces pool of available donor organs
What needs to occur to protein antigens before they can bind and be presented by MHC molecules?
Processing into small peptide fragements
Describe the presentation of antigens by MHC class I molecules. (4)
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
What occurs to the proteasome when receiving inflammatory cytokines?
Modified to produce altered peptides
Describe the role of TAP. (2)
Component of multi-protein assembly - peptide loading complex
Includes tapasin and calreticulin
Delivers peptides to MHC class I molecules
Describe binding and presentation of antigens by MHC class II molecules. (3)
Extracellular antigen degraded to peptides by acid proteases in phagolysosome
Peptide binding by MHC class II
MHC class II presents peptide at cell surface
Explain the role of the invariant chain and HLA-DM in MHC class molecule binding. (5)
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
In normal healthy cells, what other antigen sources with MHC class I and II molecules present?
Self proteins
Where are accessory molecules to antigen processing encoded?
Within the MHC gene
TAP and LMP (class I)
HLA-DM (class II)
Which cells recognise and kill cells infected with MHC class I-presented antigens
Cytotoxic CD8+ cells
Give another name for cells expressing MHC class II molecules.
Antigen-presenting cells
Which cells are activated by APC/MHC class II molecules?
Helper CD4+ cells
