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75 Cards in this Set
- Front
- Back
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Which immune system is this? Innate or Adaptive?
Very antigenic specific using T Cells and B Cells |
Adaptive
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HOw do you differentiate between a B cell and T Cell?
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the receptor it has on its surface
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B Cell Receptors (Ig) look like what and what do they recognize?
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Ig or antibody molecules that are tethered to their surface before they are activated, that recognizes soluble or intact macromolecule (proteins, lipids, polysaccharides) and small chemicals.
** these antigens *DO NOT need to be processed. |
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T/F The antigens recognized by B cells need to be processed.
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FALSE
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What do T Cell receptors (TCR) recognize?
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Will ONLY recognize processed antigen fragments presented by MHC on the surface of antigen presenting cells (APCs)
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What is a professional APC?
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Constitutively express high(er) levels of MHCII and costimulatory moleculesn on their surface and are efficient inducers of T cell responses
- APC is their 'main' purpose - *critical for producing primary response to infection |
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List the 3 main professional APCs.
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B Cell
Macrophage Dendritic Cell |
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What is the 'most selfish' professional APC? and why is it called that?
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B Cell, they are very specific and recognize antigens that they are specific for and only present antigens they are specific for.
Internalize Ag via Ig receptor *(therefore restricted to single antigenic specificities) |
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T/F B CELLS have the highest constitutive levels of the three APC
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True
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B Cells are efficient activators of CD4+ T Cells, what does CD4+ do?
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B Cells present T cells of a similar specificity - CD4+ is a helper T cell that helps the B cells do their job.
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What is a professional APC?
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Constitutively express high(er) levels of MHCII and costimulatory moleculesn on their surface and are efficient inducers of T cell responses
- APC is their 'main' purpose - *critical for producing primary response to infection |
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List the 3 main professional APCs.
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B Cell
Macrophage Dendritic Cell |
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What is the 'most selfish' professional APC? and why is it called that?
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B Cell, they are very specific and recognize antigens that they are specific for and only present antigens they are specific for.
Internalize Ag via Ig receptor *(therefore restricted to single antigenic specificities) |
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T/F B CELLS have the highest constitutive levels of the three APC
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True
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B Cells are efficient activators of CD4+ T Cells, what does CD4+ do?
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B Cells present T cells of a similar specificity - CD4+ is a helper T cell that helps the B cells do their job.
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What APC is this?
primary role: efficient endocytosis/phagocytosis of antigen Express both MHC I and MHC II - if it T cell help is necessary |
Macrophages (although at lower levels than B cells and DCs)
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What is the most impt. APC in bridging the gap btwn innate and adaptive immune response?
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Dendritic cell
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What is the primary role of a DC?
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primary function is antigen presentation
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Which APC is a VERY efficient activator of NAIVE T Cells?
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Dendritic Cells
- has high levels of MHC and costimulatory molecules |
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How do Dendritic Cells have increased contacts with T Cells?
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- extensive folds and dendritic extensions allowing for contact with multiple T Cells
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What is a "non-professional" APC?
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almost ALL NUCLEATED CELLS can become an APC after infection and activation.
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Can a non nucleated cell be a non-professional APC?
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no
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Do "non professional" APCs constitutively express MHC, which is required for naive T cell activation?
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NO - they DO NOT (majority of them)
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When do "non professional" APCs express MHC?
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only upon stimulation of the cell by certain cytokines such as INF - gamma, which up regulates MHC I
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Once a virus is processed and lysed and the fragments are shipped to be 'packaged' does it stay with MHC to the surface?
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yes, this is the only way that Cytotoxic T Lymphocytes will react - if they see the two together.
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What is the 'basic' difference between MHC I and MHC II?
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they represent the diff. pathways thru which antigens are processed and presented and also the diff. types of cells that will recognize MHC.
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What does MHC I target?
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(when there is a cytosolic, in the cell) - antigen) virally infected cells and is recognized by CD8+ T cells (CTL cytotoxic)
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What does MHC II target?
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(endocytic bacteria, outside the cell) B, DC, macrophage - which isn't infected by the antigen but has taken up the antigen. - MHC II is recognized CD4+ T cells (helper T Cells)
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What is the trimolecular complex?
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Includes: MHC, peptide and T cell receptor - all are required to actiavte the T Cell
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T/F CD8+ T Cells are MHC I restricted and recognize cytosolic or endogenous proteins.
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true
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CD4+ T Cells are MHC ___ restricted and recognize ______and intravesicular pathogens (exogenous)
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II, and extracellular
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What is MHC restriction?
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- allows individual T cells to recognize foreign Ag displayed on the surface of an individual APC
- Allow T Cells to distinguish between self and non-self - so it prevents destruction of self tissue (autoimmunity) |
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Where are T Cells generated and where do they mature?
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T Cells generated in bone marrow and mature in Thymus
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T/F Only T Cells that do not recognize self are kept - T cells that recognize self die. (that's positive selection)
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T, because you don't want the T cells to recognize self and kills self
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T/F The only antigens that are selected for positively are antigens that are specific for foreign Ag + MHC. Ag that are specific for self tend to be deleted.
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True
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T/F You don't want immune system to have too much of a response, the stronger that T cell binds to an antigen, the more it's gonna work - so it will also be deleted.
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T - things that ind with low avidity to self peptide - MHC complexes survive and TCRs that bind with high avidity die (negative selection)
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Is MHC essential for antigen presentation to T cells?
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yes -
T Cells are constnatly surveying for foreign antigen particles |
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What does it take to get a T cell response in relation to MHC and antigen
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Self MHC + foreign antigen = T cell response
Self MHC + self AG = No t cell response |
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T/F MHC is expressed or it's expression can be induced on almost every nucleated cell in the body
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true
- Viruses can infect virtually an nucleated cell so MHC I functions to alert the CD8+ T cells - MHC expression tells the immune system that the cell is a "self" cell |
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T/F MHC is a key factor in determining tissue matching for transplant donors and recipients
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True
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T/F ALL MHC in the body is "Self"
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true
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MHC molecules have a ________ (small, or broad)specificity for peptides.
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broad, i.e. many different peptides can bind within the MHC binding cleft.
unlike Tcells and Bcells |
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Peptides associated with MHC have a ___ (slow/fast) on and (slow/fast) off rate.
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slow, slow
impt. because it can roll on and stay there and it gives T Cells time to come and bind to the MHC |
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MHC molecules (do/don't) discriminate from self and foreign peptides
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DO NOT discriminate - both presented at equal frequencies - T cells differentiate
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What is a haplotype?
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basically the genotype for MHC
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What does the MHC haplotype of an individual determine?
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which peptides bind and how peptides bind
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What MHC originally linked with and then what critical importance did we find it to have?
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original function was linked only to graft rejection
- later found to be of critical importance to *all immune responses involving protein antigens |
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What is MHC known as in humans?
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HLA (human leukocyte antigen) in huma
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MHC genes are highly polymorphic - meaning?
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hundreds of alleles in humans with ~10^13 combinations (most polymorphic genes are in the human genome)
- reason why it is difficult to find transplant donors, even among first degree relatives |
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MHC are concomitantly expressed - meaning?
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ex: dominant and recessive alleles - instead - MHC all are equally expressed.
The set of MHC alleles on an individual chromosome is termed the MHC haplotype |
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Get HLA's from both parents, are they both expressed?
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yes, equally - why there is 10^13 combinations possible
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What does MHC haplotype can influence:
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haplotype is the HLA genes that you inherit and that you express.
- how an individual responds to certain pathogens (b/c diff. MHC have diff. bind affinity for diff. peptides) - susceptibility to certain diseases - transplant success |
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What does it mean to have a significatn disease and HLA Assoc.
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that some alleles are found in diff. percentages in pt's with particular disease
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What are the 'general points' of antigen presentation/
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- multiple cell types are brought into pay to initiate ag presentation
- a series of molecular interactions takes place to present small fragments of protein antigens to T cells - Antigen presentation is modulated by co-stimulatory molecules - need these for response - Successful antigen presentation results in activation of T Cells - the end goal |
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What is an antigen?
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an antigen is any substance that can be specifically bound by an antibody or TCR
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What are the diff. types of antigen?
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Immunogen - an antigen that ellicits an immune response
Tolerogen - induces immunological tolerance or immune non-responsiveness Allergen - an antigen that cuases an immediate hypersensitivity (allergic) reaction |
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Elaborate on how a toleragen works
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some drugs are used as tolerogens - they tell body to not attack certain substances (ex: orally eating food vs. injecting the food)
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How do you tell the difference between an endogenous antigen and an exogenous antigen/
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Endogenous - antigens generated within the cells fo the body as a result of normal metabolism or viral infections
Exogenous Antigen - ag. directly entering the body from the environment |
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What are some examples of endogenous antigens vs. exogenous?
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endogenous:
- proteins encoded for by genes of viruses - abberant proteins encoded for by mutated genes (e.g. cancer cells EXogenous: - Inhaled antigen (cat hairs, pollen) - INgested antigen (shellfish protien, peanuts) - INjected antigen (splinter, injected vaccine) |
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Which antigen (ex or end) are processed via the MHC I pathway and presented to CD8+ T cells?
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Endogenous
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Which antigens (ex or end) are processed via the MHC II pathway and presented to Cd4+ T Cells?
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Exogenous
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What are the 5 basic steps in antigen processing?
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1. Tagging the antigen for destruction
2. Proteolysis of Antigen 3. Peptide delivery to MHC molecules 4. Peptide binding to MHC molecules 5. Display of MHC-peptide complexes on APC surface |
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How do B cells, DC and macrophages engulf the antigen?
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B cells: receptor mediated endocytosis
DC: pinocytosis Macrophages: phagocytosis (receptor mediated |
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Where does 'tagging' occur?
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in the endocytic vesicle with antigen within it.
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Where does processing occur?
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after the endocytic vesicle as fused with the lysosome and is now an endolysosome. = breaking down of antigen
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What is occuring after the protein is being broken down in the endolysosome?
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the MHC is being biosynthsized in the ER and then will be transported from the Golgi (with the invarient chain) via exocytosis to the endolysosome
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What is the invariant chain and why is it impt?
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once the MHC molecule is made the invariant chain will bind in the MHC and prevents it from binding to anything else before it reaches the peptide fragments to bind.
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What is DM's role?
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Cleavage of the invariant chain (CLIP) and allows antigen to enter MHC
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What happens once MHC and antigen fuse?
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they are brought to the surface of the cell and expression on surface.
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Where are the proteins located in MHC I processing?
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in the cytosol
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What is ubiquitination?
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the viral protiens are tagged by ubiquitination - what tells the proteosome to break it down
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The proteins once broken down they will be transported from cytosol to ER what is their chaperone?
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TAP is the chaperone for the protien fragments
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Once TAP and viral protein fragment reaches the ER what happens?
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there is already processed MHC I and it binded together in ER and then leaves via the golgi through exocytotic vesicle and there is then surface expression of peptide-class I complexes (MHC +viral protein)
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What is an epitope?
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a peptide fragment that binds an MHC molecule for recognition by TCR
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What is an immunodominant epitope?
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the epitope for which most of the responding T cells in a given individual is specific
- typically correspond to the peptides proteolytically generated within APCs that bind most avidly o MHC molecules and stay there the longest |
