Antigen structure and Interactions with Antibody II

What is valency?

It is the number of sites that an antibody can bind to

What are the two types of multivalent antigens?

1. Multivalent antigen with different epitopes

2. Multivalent antigen with a repeated epitope

Does antigen valency contribute to immunodominance?

Yes it does

What can T cells recognize?

Peptides complexed with self-MHC molecules on the surface of antigen-presenting cells and other nucleated cells

What are T cells typically?

Internal and contain amphipathic peptide sequences revealed by antigen processing

Why are T cell epitopes amphipathic?

This is because the hydrophobic amino acid residues interact with MHC molecules while the hydrophilic amino acid residues interact with the T cell receptor

What is immunodominance of T cell epitopes determined by?

The ability to interact with MHC molecules of a given individual (MHC molecule diversity)

What can certain T cells recognize?

Lipids and glycolipids presented by CD1

What do all nucleated cells in the body express?

MHC Class I

Describe the structure of the TCR. What does it interact with?

It is a heterodimer and has no inherent signalling by itself which is why it interacts with the CD3 chains

Describe what happens when TCR binds to the right antigen via MHC

1. Antigen will bind to TCR on presentation by MHC

2. A signalling pathway will be generated

3. The TCR is stabilized by a CD4 coreceptor on the plasma surface of a T cell which is binding to the TCR in an area other than the antigen-binding site

4. Lck is brought into proximity which is a kinase that will phosphorylate itself and then phosphorylate the CD3 chains

5. Now acts as a docking site for kinases

If you inject mice with hen egg-white lysosome what happens?

Antibodies against the hydrophilic regions will get produced and the immunodominant peptide for T cells will be AA 64-80 that they will bind to

What are mitogens? What are they known as?

They are capable of activating many clones of B cells or T cells irrespective of their antigenic specificity and are therefore known as polyclonal activators. (Can activate large numbers of B and T cells non-specifically)

What is lectin concanavalin A?

It is a plant protein and mitogen that will preferentially activate T cells

What is LPS?

It is a mitogen that will preferentially activate B cells

What is a bad thing associated with mitogens?

If all the B and T cells become activated non-specifically then they will use up all the growth factors as there are a limited amount per cell type. Most of them will not see the pathogen and then you cant get specific cloning expansion

What are super antigens?

They activate large numbers of T helper cells by cross-linking their TCRs with any MHC Class II molecule on an antigen-presenting cell and are therefore extremely potent T cell mitogens

What is an example of a super antigen?

Staphylococcal enterotoxins

Describe how super antigens work

1. Have a MHC II on an APC presenting an antigen

2. It is not the peptide that the T cell is specific for

3. Have an endogenous superantigen in the APC that will bridge the MHC II to the TCR

4. It is an artificial linkage that forces the two complexes to come together and now the T cell is activated

What are antigen-antibody interactions mediated by?

Relatively weak forces that depend on the close approach of both molecules and four different types of interactions

What are the four different interactions that mediate antigen-antibody interactions?

1. Ionic or electrostatic interactions

2. Hydrogen bonding

3. Hydrophobic interactions

4. Van der Waals interactions

What further increases the magnitude of the weak atomic forces?

Exclusion of water molecules at the site of interaction

Is the interaction between an antigen and antibody reversible?

Yes it is because it does not form a covalent chemical bond

Are all the forces weak?

Yes but together they are strong

What is van der Waals interactions based on? Describe what happens

Proximity. If molecules are able to get close enough then the electron clouds are able to interact and you’ll have a non-specific interaction. It is also able to exclude water molecules from the site of interaction

Do different antibodies have different affinities for an antigen?

Yes

What is affinity?

It is the strength of the sum total of non covalent interactions between a single epitope and an antigen binding site of an antibody

What is avidity?

It is the overall strength of binding between a multivalent antibody and a multivalent antigen

Is the avidity of IgM greater than IgG? What about affinity?

Avidity is greater but affinity will be the same

Do non-covalent interactions mean they are either on or off? (antibody and antigen binding)

Yes

Does a higher affinity mean that they are more likely to be bound?

Yes

Can receptors have the same affinity but different avidity?

Yes