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Specific Defenses of the Host
Part 3
(acquired or adaptive immunity)
Mechanisms of the Immune
Response, continued
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How do MHC class II molecules function?
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MHC class II antigens – these molecules bind foreign
antigens that have entered the cell via endocytosis.
They trigger an immune response by stimulating helper
CD4+ T cells.
Both the binding of the T cell receptor to the MHC class
II molecule and the peptide as well as the binding of the
CD4 molecule to the MHC class II molecule are required
for stimulation of the T cell.
The genes that encode MHC Class II molecules are
called immune response genes and they determine
whether an individual can mount an antibody response
to T-dependent antigens.
Presentation of
Foreign Antigens
Made Outside the
Cell to CD4+ T Cells
Presentation of Foreign Antigens
Made Outside the Cell to CD4+ T
Cells
MHC Class II Interaction with
CD4+ T Cells
MHC Class II Interaction with
CD4+ T Cells
Mechanisms of the Immune
Response, continued
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The MHC class II molecules, like the class I
molecules, consist of two polypeptide chains called
alpha and beta.
Both the alpha and the beta chain are encoded in
the MHC class II region.
There are 3 functional loci – DR, DQ, and DP.
Each locus encodes an alpha chain and a beta
chain.
In your assay, you will be amplifying a region of
the HLA DQ alpha chain.
Human MHC Class II Region
Mechanisms of the Immune
Response, continued
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Since one inherits (assuming heterozygosity), 6
different loci, and since each locus encodes both an
alpha and a beta chain, individuals can express 1020 different MHC class II molecules/cell.
DR, DQ, and DP beta chains associate mainly with
alpha chains from their own family.
The alpha and beta chains can be divided into 4
separate domains or regions: the peptide binding
domain, immunoglobulin-like domain,
transmembrane domain, and cytoplasmic domain.
The
Structure
of the
MHC Class
II
Molecule
Mechanisms of the Immune
Response, continued
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The peptide binding domain
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This region is made from alpha 1 and beta 1 with a
structure similar to that of class I molecules – an 8stranded beta sheet plus 2 alpha helices creating a cleft
for peptide binding.
In terms of the peptides they bind, since the ends of
the cleft are open, bound peptides can extend beyond
the cleft.
The peptides that bind to the MHC class II molecules
can range in size from 10-30 amino acids.
Mechanisms of the Immune Response,
continued
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Each MHC class II molecule can bind more than 1 different
peptide, but as with the class I molecules, all peptides that
bind a single class II molecule will share structural
features.
The MHC class II molecules therefore, are said to bind their
peptides with loose specificity.
All polymorphic residues are found within the cleft where
the peptide binds or where the T cell receptor interacts
with the MHC class II molecule. Differences here provide
the basis for T cell restriction.
The class II molecules are not as polymorphic as the class
I molecules.
In this class you will be amplifying the polymorphic region
of the HLA DQ alpha chain.
Polymorphisms
within the MHC
Class II
Molecules
Mechanisms of the Immune
Response, continued
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The immunoglobulin-like domain
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The transmembrane domain
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This is the region where the T cell CD4 molecule
interacts with the MHC class II molecule (at the
beta 2 region).
This domain does not affect the extracellular
domain of the molecule.
The cytoplasmic domain
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This domain has an unknown function.
Mechanisms of the Immune
Response, continued
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Intracellular class II molecules have a gamma or
invariant chain associated with them to prevent
endogenous peptides from binding.
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The invariant chain is removed upon the fusion of an
endosome with an exocytic vesicle containing an MHC
class II molecule.
The exogenous peptides are then loaded onto the MHC
class II molecule.
In summary:
The
Structure
of the
MHC
Class II
Molecule
Presentation of Foreign Antigens
Made Outside the Cell to CD4+ T
Cells
MHC Class II Interaction with
CD4+ T Cells
MHC Class II Interaction with
CD4+ T Cells
Mechanisms of the Immune
Response, continued
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Located between the class I and the class II genes
are genes whose expression is necessary for
efficient assembly of class I molecules.
This includes the genes that encode the TAP
proteins that function in transport of proteins (or
peptides) from the cytosol into the ER where they
can associate with newly formed class I molecules.
Genes that encode the cytosolic protease complex
proteins are also found there as are the genes that
encode the complement components.
Presentation
of Foreign
Antigen
Made Within
the cell to
CD8+ T
Cells
Which MHC
Class is this?
T-independent antigens
revisited
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What is the hypothesis regarding why Tindependent antigens can stimulate B cells
without the help of T cells?
Conversely, why can’t T-independent
antigens enlist the help of T cells?
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Hint: what is required to stimulate a T cell?