Lecture 9 - MHC Flashcards
Why do we need T cells?
CTL: once viruses get into cells, we need a way of detecting this and killing off the cells
Ab’s are only good for blocking them before they gain access
What are the two types of T cell?
Cytotoxic T cell:
• killing of infected / transformed cells
• CD8+
‘Helper’ T cells:
• help B cells & macrophages
• CD4+
What are the CD molecules?
“Cluster of differentiation”
• Found on only subsets of leukocytes
• Classify the cell and/or stage of differentiation
What does MHC stand for?
Major histocompatibility complex
How are T cells ‘activated’?
Angtigen presented to their TCR’s by APC’s using MHC’s
CTL: MHC I
T helper cells: MHC II
What sort of epitopes can TCR’s bind?
Only short, linear epitopes
• 8-11 aa long
Must be present by an APC
What are the regions on the MHC I molecule?
- Peptide binding region
- Ig like region
- Transmembrane region
- Cytoplasmic region
- α1
- α2
- α3
- β2
What are the regions on the MHC II molecule?
- Peptide binding region
- Ig like region
- Transmembrane region
- Cytoplasmic region
- α1
- α2
- β1
- β2
Which accessory molecules do CTL and Th cells have?
CTL: CD8
Th cells: CD4
Describe the specificity of TCR’s
Specific for:
• peptide
• MHC
On which cells are the various MHC molecules expressed?
MHC I: all nucleated cells
MHC II: antigen presenting cells: • mϕ • DC's • B cells • Langerhan's cells
Expression upregulated:
• during immune response
What is the genetic locus that encodes MHC in humans?
And in mice?
HLA locus
• Human Leukocyte Antigens
Mice:
H-2 locus
Describe the structure of the MHC locus
Draw this
• Locus contains regions
• Regions contain genes
S25
Which genes code for MHC I in humans?
B
C
A
Which genes code for MHC II in humans?
DP
DQ
DR
Which genes code for MHC I in mice?
K
D
Which genes code for MHC II in mice?
I:
• I-A
• I-E
What is the difference between ‘polymorphism’ and ‘allele’
Allele: version of a gene
Polymorphism: existence of different alleles
What is the notation for the various HLA alleles?
Numbered system: each allele has different number
e.g.
• HLA-A2
• HLA-DR5
What is a haplotype?
Compare this to genotype
Haplotype: Grouping of different alleles found on a given chromosome (i.e., just one of the chromosomes)
Genotype: alleles present within an individual, i.e. alleles on both chromosomes
What can be said about the haplotype of inbred mice?
Will be the same as the genotype
What is the heavy and light chain of MHC I?
Heavy: α1, α2 & α3
Light: β2-microglobulin
How many extracellular domains on MHC I?
How about MHC II?
4 extracellular domains in each
Describe the peptide binding cleft in MHC II
α1 & β1
Describe the association between the alpha and beta chain of MHC II
Not covalently bound
What are TCRs specific for?
Specific for:
• peptide
• MHC
Where does the peptide antigen bind to MHC?
Peptide binding groove
Describe the pattern of expression of HLA genes
Co-dominant
• both alleles expressed simultaneously
What is the nomenclature for mouse MHC alleles?
Letter superscripts
eg.
H-2 K^b
In humans, which is more complex: haplotype or genotype?
Genotype is more complicated, because it concerns genes on both chromosomes
Are MHC genes polymorphic?
What does this affect?
Yes, very much so.
There are as many as 100 different alleles for some HLA genes
This affects:
• peptide binding cleft
• TCR binding
How can CTL’s recognise infected cells (in general)?
Infected cell is expressing molecules on their cell surface
How are the heavy and light chains associated in MHC I?
Not covalently bonded
Describe the peptide binding cleft in MHC I
α1 & α2
Describe the association between the alpha and beta chain of MHC II
Not covalently bound
What is important about CD4?
- Found on Th cells
- Recognises the MHC II molecule
- binds to β2 domain
What is important about CD8?
- Found on CTL
- Recognises MHC I molecule
- binds to α2 domain
Where is β2-microglobulin encoded?
Chromosome 15
What is the nomenclature for mouse MHC alleles?
Letter superscripts
eg.
H-2 K^b
What is meant by: ‘MHC molecules are restricted’?
They are highly specific for certain TCR and peptides
Which MHC do TCR’s recognise?
A given T cell will only recognise ONE of the MHC molecules in an individual
On which chromosome are the HLA genes?
HLA class I and II: Chromosome 6
β2m: Chromosome 15
Where are the disulphide bonds in the following: • MHC class I • MHC class II
MHC I:
• Within all domains (α1, α2, α3 and β2m)
• NB there are no disulphide bonds between the α and β chains
MHC II:
• No disulphide bonds between either the chains or within domains
Describe the changes to MHC expression during an immune response
MHC class I & MHC class II expression upregulated during an immune response
The binding pockets of MHC molecules is altered by…
Polymorphism
If one only has a maximum of 6 versions of both MHC class I & II, how can all the different epitopes be presented on these molecules?
Epitopes have anchor residues that are conserved
These common anchor residues bind into the binding pockets of the peptide binding cleft of the MHC molecule
