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L11 – Antigen presentation and the MHC
The MHC comprises a set of genes, several of which encode surface proteins
that present peptide antigens to T-cells
...
In humans, it is called HLA (Human Leukocyte Antigen),
whereas in mice, it is known as H2
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There are two main classes of MHC
...
MHC
class I molecules are specialized for alerting cytotoxic T cells to the presence
of an infection inside a cell
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The human MHC is called Human Leukocyte Antigen (HLA)
...

The MHC gene locus can be divided into 3 classes, classes I, II, and
III
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In humans, there are three types of MHC class I, HLA-A, HLA-B and
HLA-C and three types of MHC class II, HLA-DP, HLA-DQ and HLADR
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Between the class I and II genes is the class III genes
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However, some genes encoding
products important for immune responses are found within the MHC
class III gene segment
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In the mouse, MHC is referred to as H2 and is found as a linked series
of genes on chromosome 17
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For example, the MHC class I genes in mouse are not all
closely linked together but are found in two groups which are separated
from each other by the MHC class 2 and class 3 genes
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For
example, well over a thousand different nucleotide sequence variants of HLAA have been described
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• For MHC class I, HLA-B is the most variable, followed by HLA-A and
then HLA-C
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MHC genes are co-dominantly expressed so that the variant of for example
HLA-A inherited from both parents will both be expressed
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The same co-dominant expression is seen with the MHC class II
molecules
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• It is comprised of a highly polymorphic α polypeptide chain of 44kDa
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• This α chain is linked to the smaller, non-polymorphic, 12kDa
polypeptide called β-microglobulin
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• The β-microglobulin and α3 regions of the MHC class I molecule fold
into what resemble an immunoglobulin domain
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• The peptide-binding groove of MHC class I molecules is closed at both
ends, thereby allowing it to occupy smaller peptides
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• It is comprised of a 34kDa α polypeptide organized into two globular
domains (α1 and α2) and a 29kDa β polypeptide chain, also organized
into two globular domains (β1 and β2)
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• α1 and β1 (distal to surface) form two extended helices above a βpleated sheet, similar to the α1 and α2 of MHC class I
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• The peptide-binding groove of MHC class II molecules is open at both
ends, thereby allowing it to occupy larger peptides
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• The peptides that bind to MHC class I are derived from endogenous
antigens
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N-terminus of bound peptide is tightly hydrogen-bonded to conserved
residues at one end of the groove, whilst the C-terminus will engage in
hydrogen binding and ionic interactions at the other end of the groove
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It is only the amino acids at these positions that will critically determine
whether binding will occur
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To MHC class II
• MHC class II molecules present peptides of 15 amino acids or longer in
length
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• Class II groove residues hydrogen bond and use other non-covalent
interactions along the entire length of the peptide
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For most MHC class II haplotypes examined
to date, there appear to be 3 critical anchor pockets
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g
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Peptides of 8-10 amino acids long are then transferred from the cytosol
to the endoplasmic reticulum by the transporters of antigenic peptides,
TAP1 and TAP2, which are members of the ATP-binding cassette
(ABC) family of ATP-dependent transport proteins
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One of the many constituents of the PLC complex is ERp57 (57kDa ER
thiol oxidoreductase),which isomerizes disulphide bonds to ensure the
correct conformation of the MHC molecule
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It then traverses the Golgi system
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Exogenous
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An exogenous antigen is an antigen that has been endocytosed or
phagocytosed from outside of the cell and is processed by proteases in
the acidic endosomal vesicles
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The peptides that are generated are around about 15 amino acids or
even longer
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The MHC class II molecule is transported to the trans-Golgi reticulum,
following which it it enters a class-II containing vauole that fuses with
the endosome containing the peptide
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The peptide-MHC complex is then taken to the cell surface for
presentation to CD4+ T- cells

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