Lecture 9 - Babiuk Flashcards
(57 cards)
Define antigen.
Any molecule large enough to be presented to the immune system on which there is a functional epitope. Can be self or non-self.
Define epitope.
The functional portion on the antigen that is recognized by the immune system’s B or T cell receptors.
What kind of epitopes are recognized by B cells?
T cells?
B cell epitopes can be linear or confirmational.
T cell epitopes are linear and can be recognized by either CD4+ or CD8+ cells
What are T cell independent antigens
Antigens that do not require T cells to activate B cells. They are usually large polymeric molecules with repeating antigenic determinants like bacterial polysacharides
What is the difference between an antigen and a superantigen?
An antigen is recognized in the MHC groove and requires V and J alpha as well as V, D, and J beta. Very low frequency of antigens.
A superantigen is recognized by Vbeta alone and is a high frequency of antigens. They are recognized outside of the MHC groove.
Define hapten.
A small chamical group that is immunogenic only when bound to a carrier antigen. It is too small for stimulation on its own in a mouse but if injected along with BSA it would activate the immune system.
How many TLRs are there in humans? What do they recognize and how did they get their name?
11.
They recognize Pathogen Associated Molecular Patterns
Toll gene in Drosophila (is similar)
What do the following TLRs recognize? TLR 3 TLR 4 TLR 5 TLR 6 TLR 9
ds RNA LPS Flagellin Lipopeptides CpG motifs
Why are everyone’s MHCs different from one anothers?
To protect at the population level.
Briefly describe MHC I structure
Comprised of MHC class I heavy chain containing 3 domains and B2 microglobulin (beta). All held together by disulfide bonds.
What is the function of B2 microglobulin?
It is essential for the expression of all MHC class I molecules at the surface. B2 microglobulin KO mice do not have MHC class I molecules.
Where is the peptide binding groove in MHC I? What size peptide can it accomodate? On what does this depend?
Between alpha 1 and alpha 2 domains.
8-10 amino acid residues in length
Variations in AAs at key residues in binding domain change the shape of the binding groove which changes the peptides that will bind to it.
What are anchor residues?
What can they help to predict?
Anchor residues are residues that need to be met at matched in the MHC by peptides in order for binding to take place.
Anchor residues are able to predict peptide binding using computer algorithms.
What parts of the TcR come in contact with the MHC?
The TcR contacts the polymorphic residue regions of the MHC molecule as well as the residue of the peptide presented.
Briefly describe the structure of the MHC class II molecules.
What size peptide can it accommodate?
On what does this depend?
How is this different from MHC I?
Consists of heterodimers of heavy (alpha) and light (beta) glycoprotein chains.
10-15 AAs in length
Variations in AAs at key residues in binding domain change the shape of the binding groove.
The MHC II has a more open binding groove allowing the recognition to be several AAs longer to present to CD4+ T cells
Where is the peptide binding cleft located on MHC II?
Between the alpha 1 and beta 1 domains.
Briefly describe the genomic organization of the MHC in humans.
How many MHC genes do other animals have?
Mediated by the human HLA which has, in order, the class II, class III, and class I MHC loci. Other animals have varied amounts of MHC genes.
What are mixed lymphocyte reactions?
They are reactions with two lymphocytes that have been mixed together and their Tcell/MHC portions will react together and create a reaction on their own.
Where are class I MHCs expressed? What is their function? Where are class II MHCs expressed? What is their function?
Class I are expressed on almost all nucleated cells (except hair follicle cells) and act as spies to communicate what is happening inside a cell.
Class II are expressed only in cells responsible for generating immune responses (macrophages, neutrophils, monocytes, B cells)
Define co-dominant expression.
What kind of molecule is co-dominantly expressed in human immune systems?
How many molecules of this kind are present?
Why is this important?
Both parental alleles of each gene are expressed.
The MHC molecules are co-dominantly expressed on the surface of cells.
3 from mom, 3 from dad = 6 total possibilities but since alpha and beta chains can rearrange, more than 6 are possible.
This increases the number of different MHC molecule possibilities that can present peptides to T cells.
What significance does the broad specificity of the MHC hold for humans?
Many different peptides can bind to the same MHC molecule
What significance does the single peptide presentation at a time of the MHC hold for humans?
Each T cell responds to a single peptide bound to an MHC molecule.
What significance does binding only peptides via the MHC hold for humans?
MHC restricted T cells respond only to protein antigens and not to other chemicals.
Peptides are acquired during intracellular assembly in the MHC. What significance does this hold?
Class I and class II MHC molecules are able to display peptides from different cellular compartments.
