LET THYIS BE THY GUIDSE
What cells dictate what the challenge of the immune system is going to be?
What is required for T cell to interact with epitope?
- MHC molecules are essentially ____, in that they present epitopes to the ______ - to see idf somthing needs to be done
- T cells
- cops, judge (T cells)
- Can T cells see whole antigen?
- If cytotoxic T cells have a receptor that recognizes the epitope - what will happen?
- endogenous are type what?
- How can cytotoxic t-cell be represented?
- How can helper T-cells be represented?
What type of T cell does MHC class 1 hook up with?
What type of T cell does MHC class 2 hook up with?
- No it must be processed and then presented on MHC molecule
- it will kill the cell presenting the epitope via MHC
- Tc, CTL, CD8+
- TH, CD4+
- Cytotoxic T cell (CD8)
- Helper T cell (CD4)
(MAJOR HISTOCOMPATIBILITY COMPLEX)
- A system of gene products used for ______ recognizing and _____ foreign antigens. These antigens can be from within host cells (____) or from extracellular sources (_____). Both self and non-self antigens are constitutively ____ and _____.
The system function to recognize a wide variety of epitopes:
_____ - several genes exist for a given MHC class
_____ - a large number of allels exist for a given gene
_____ - will bind a range of similar epitopes
- Except for the ____ locus, each locus has many ____. Each allele can present processed antigens to T cells
- T and B cells have evolved to recognize any antigen (within an _____) - MHC hasn't for every individual - but has for a given _____
- specifically, eliminating, endogenous, exogenous. processed and presented
- DRa, alleles
- individual, population
_____ - encode a single chain - present endogenous genes to _____
_____ - encode two chains - present exogenous genes to _____
_____ - encode which five things?
Strange thing about MHC complex is that the different regions have been shuffled in different ways across different species - but that the whole region has stayed intact.
All verterbrates possess MHC genes, but the _____ of genes within each class varies. Many ______ exist within the locus.
- Class I, cytotoxic T cells
- Class II, helper T cells
- Class III, cytokines, heat shock proteins, Ag processing, transport proteins, complement proteins
- number, pseudogenes
Class I and II MHC molecules _____ present the antigen on the surface of the cell. _____ is a loose term for all otehr genes in the MHC region.
Many of the class III genes econde proteins involved in ____ and ____. Other genes encode ____ and ____. Interestedingly, several ______ receptors are encoded in this region and may influence ___ secltion.
- physically, Class III
- processing, transport, complement, cytokines, mate
(MHC CLASS 1 STRUCTURE)
- _____ expressed on the surface of ___ nucleated cells
- encodes a _____ AA non-covalently associated with _____ (what is thsis purpose).
Which domains form the pocket?
- constitutively, all
- single, B2-microglobulin (B2m), structural
- alpha 1 and 2
(MHC class 1 structure)
1 side of hotdog bun = _____
second side of hotdog bun = ____
hotdog = ____
- alpha 1 domain
- alpha 2 domain
(MHC Class-I function)
- Because this class communicates with cytotoxic T cell - it causes ____
- Class I recognition is especially important for _____. The ____ proteins are produced within the host cell and are displayed on the surface in context ith MHC class 1.
- cell death
- virus-infected cells, viral
(MHC class II antigens)
- expressed primarily on _____.
- Consist of _____ polymorphic chains (alpha and beta) that fold together to form a _____ for processed antigens
- one side of hotdog, other side, hotdog
- two, binding pocket
- beta 2 domain of the beta chain, alpha 1 domain of the alpha chain, processed antigen (epitopes are a little larger 8-16 AA)
- The MHC binding pocket is much more _____ thatn the Ab or TCR binding pocket. Essentially, there are many _____ that fit, requiring only the conservation of the _____ that interact with the antigen ______ withing the MHC binding pocket
- Even though there are only a few pockets - can still recognize many difernt antigens
- flexible, peptides, anchor residues, contact
(MHC Class II - FUNCTION)
- present ___ Ag to ____
- This activates the _____ for the purpose of inducing the immune response, including ____, _____, and _____.
- exogenously produced, Helper T Cells (CD4)
- T helper cells, antibody production, marcophage activation, cytokine cascades
- The MHC class I binding pockets hold ____ AA while class II holds ____ AA
- they also have ____ specificity
- 8-12, 13-20
(MHC ARS Hypermutation sites)
- In orde to generate populations with the ability to present almost every possible _____, the MHC has a ___ rate of mutation (many _____) in the peptide biding cleft. This changes the specificity between _____ as to the exact structure that will fit into the cleft.
The most varaiation of MHC occur in the _____.
- antigen, high, alleles, alles
- binding pocket coding sequences
What species have limited MHC diversity? what does this mean?
- cheetahs, tasmanian devils (facial tumor) , giant pandas
- limited diversity can put populations at risk
(MHC Class II - Codominant Expression)
How many loci do you have for MHC II?
Thus, ____ versions of DR MHC class II proteins for each loci.
Because humans have 2 loci - it means they will have ___ versions of binding pockets.
DRalpha ____ interact with DQbeta
(CLASS I MHC)
- MHC genes inhereited in _____ fashion
this means they have
______ - means most people are heterozygotes (more than one allele)
_____ - when multiple genes contribute to particular phenotypic character
So what fold variety do you have for MHC class I pockets?
- two (DQ and DR)
- six fold
- MHC Class 1 has ____ fold variety in binding pocket? Class 2?
- 6 fold, 8 fold
(Heretability of MHC Alleles)
- Linkage of MHC alleles with ______ susceptibility traits or ______ pathologies is widely recognized. Various alleles can lead to presentaion/non-recognition of certain _____. MHC loci are inherited in classic ____ fashion, just like every other locus.
The high number of alleles assures that most individuals are _____ at each of the MHC loci.
How many MHC class I and class II molecules are on the surface of each cell? What are most occupied by? Are empty MHC molecules stable?
- specific disease, autoimmune, epitopes, Medelian
- 50,000-100,000, normal or self-antigens, not stable
- Antigens must be _____ before loading into MHC molecules
- Processing generates multiple ____, ____ of which can bind to class II allele
- A given cell or antigen-presenting cell will have many different ____ displayed on its surface, including _____. Only if a ____ with the correct receptor encounters that epitope, in the context of MHC molecules, will a _______ be initiated.
Why is it okay to present self epitopes (these are endogenous - so whatever MHC that corresponds to)
Cells always have MHC class ____ on the surface
- peptides, one
- epitopes, self peptides, T cell, specific immune response
- T cells don't recognize these
- MHC class I molecules are expressed by _____
- MHC class 2 are expressed primarily by _______
- What are professional antigen presenting cells (Professional APC)? What do they do?
What do these present alot of? What do they interact most directly with?
What is another cell that expresses MHC II?
- every nuceated cells
- white cells
- B cells, Macrophages, Dendritic Cells -- they are in the active process of examining the environment around the cells
- MHC class II, T cells
- thymc epithelium
- The MHC influences whether or not antigen-specific immune responses will occur. There are many examples of autoimmunities linked to the presence of specific alleles for MHC genes.
- In animals the MHC is linked to both ____ and _____ traits.
- immune, production
MHC Restriction - A given T cell receptor will only recognize _____ presented by a particular (_____) MHC molecule. That is, T cells educated in one MHC allele/epitope ______ interact with APC unless it expresses that allele bearing the _______.
- So T-cell receptor specificity is determined by a specific _____ and a specific ______.
- alleles are two different versions of the same _____
- Antigen, self, will not, same epitope
- epitope, MHC allele
(ANTIGEN PROCESSING AND PRESENTATION)
- any molecule capable of inducing antibody generation
- also called an antigenetic determinant, it is the portion of a larger antigenic molecule that is recognized by antibodies or T cell receptor
- The degradation of proteins into peptides that can bind MHC molecules for presentation to T cells
- The display of antigens as peptide fragments bound to MHC molecules on the surface of a cell
- Highly specialized cells that can display processed antigen as peptide fragments on the cell surface
- When we talk about APC we really mean Professional APC
- antigen processing
- antigen presentation
- antigen-presenting cells