lecture 3 - TCR and MHC Flashcards
T celld come out the bone marrow and go to the
thymus where the gene segments are rearranged
generation of diversity of TCR
multiple V, D and J gene segments
combinational diversity between V, D and J
junction diversity
does somatic hypermutation happen in TCR
no
TCR alpha chain formation (similar to Ig light chain):
DNA breaks between V and J
random V and J join, then they join to a constant region
TCR beta chain formation (similar to Ig heavy chain):
VD and J regions join and then to a
constant region
what chromosome are TCRalpha genes on
14
what chromosome are the TCRbeta genes on
7
what chromosome is the Ig heavy chain on `
14
what chromosome if the Ig light chain on
2 for kappa
22 for lamda
TCRgamma and YCRdelta form a slightly different receptor.
so a TCR will either be TCR alpha and beta or
TCR gamma and delta
what chromosome is TCR gamma on
7
what chromosome is TCR delta on
14
differences between MHC and TCR/BRC
there no gene rearrangement in MHC molecules
MHC molecules are expressed co-dominantly (MHCs from both chromosomes are expressed)
APC examples
B cells, macrophages, dendritic cells
MHC is located on what chromosome
6
class I MHC molecules are
HLA-A, B and C
class II MHC molecules are
HLA-DP, DQ and DR
HLA-DR has 2
beta chains
MHC are the most polymorphic genes known meaning there’s lots of
alleles
a single cell can have up to how many different MHC molecules
12 (if they are heterozygous for all 6 MHC loci)
where is most of the polymorphism
in the part of the MHC molecule that forms peptide binding groove (alpha 1 and 2)
high levels of polymorphism allows
binding of vast range of peptides that can be presented to T cells
downside with high polymorphism
increase risk of many auto immune mediated disease (e.g. presenting self antigens)
also makes donor organs for transplantation very complex
how do peptides end up bound to MHC molecules
antigen processing and presentation
peptides from antigens inside the cell (e.g virus) are usually presented by which MHC
class I
peptides from exogenous antigens (e.g bacteria) are presented by which MHC
class II
presentation by MHC class I:
intracellular antigen is broken down into peptides by
proteasome
peptides transport into endoplasmic reticulum and peptide binds to
MHC class I
MHC is then presented at cell surface with the
peptide
what are the peptides transported to ER by
TAP transporter
what complex holds the MHC in the ER until peptide is bound
PLC (peptide loading complex)
presentation by class II:
takes up antigen into a
endocytic vesicle
peptides are produced and what fuses with the endocytic vesicle
vesicle containing MHC class II
peptides bind to MHC class II and MHC is
presented at the surface
what does the invariant chain do
forms a complex with MHC class II
what does this complex do
blocks the binding of peptides when class II is being made
when is the invariant chain is the cleaved
when it fuses to the endosome as its acidic
what does this cleavage leave bound to the MHC class II
CLIP (a short peptide fragment)
what binds to the MHC class II releasing CLIP
HLA-DM allowing peptides to bind and the MHC goes to the cell surface
in normal healthy cells MHC I and II will present peptides from self proteins to show what it looks like when its healthy so can see changes if its infected
HLA-DM and TAP are coded for within the
MHC
