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Flashcards in L7: Antigen Processing and Presentation Deck (42)

How do B cells "see" antigen?

Antibody on B cells or free antibody can recognize intact antigen (i.e. soluble antigens and cell surface antigens)

Proteins, nucleic acids, polysaccharides, lipids, and small molecules are antigenic for B cells

Can recognize conformation or linear epitopes: consecutive amino acids on a denatured protein would be a linear epitope; a 3-D structure would be a conformational epitope (could even be non-contiguous amino acids when they start to overlap)


How to T cells "see" antigen?

Recognize protein antigens as discrete peptides

Recognize linear epitopes (don't recognize non-contiguous epitopes)

Recognize antigen only when it is bound to MHC


How do CD8+ cytotoxic cells "see" antigen? How do they respond?

"See" antigen complexed to MHC class I and respond by killing the infected cell


How do CD4+ helper cells "see" antigen? How do they respond?

"See" antigen complexed to MHC class II and respond by proliferation and production of cytokines


What must APCs express in order for T cell to recognize and respond to a foreign peptide antigen?

APC must express MHC molecules that are recognized as self


What are "self" MHC?

Those MHC antigens that the T cell encountered during development in the thymus


What are cytosolic pathogens presented to?

Presented to effector CD8 T cells

Effect is cell death


What are intravesicular pathogens presented to?

Presented to effector CD4 T cells

Effect is activation to kill intravesicular bacteria and parasites


What are extracellular pathogens and toxins presented to?

Presented to effector CD4 T cells

Effect is activation of B cells to secrete Ig to eliminate extracellular bacteria/toxins


What recognizes exogenous antigens?

CD4 cells

These antigens are processed and presented w/ MHC class II

The CD4+ T cells respond with proliferation and cytokine production


What are the professional antigen presenting cells? What do they do?

Dendritic cells


B cells

Either express constitutive MHC class II or very easily upregulate it

Antigen presenting cells are those special cells that can provide the high levels of MHC and co-stimulatory molecules required for T cell activation


What is the response of dendritic cell antigen uptake?

Naive T cell activation: clonal expansion and differentiation into effector T cells


What is the response of macrophage antigen uptake?

Effector T cell activation: activation of macrophages (cell-mediated immunity)


What is the response of B cell antigen uptake?

Effector T cell activation: B cell activation and antibody production (humoral immunity)


Where are dendritic cells found?

Found at all of the sites where there will be antigen entry

Skin: Langerhans cells and layer of dermal dendritic cells

GI tract

Respiratory tract


What occurs if antigen enters blood stream?

It is filtered out in the spleen and presented to T cells in the spleen


Compare the functions/properties of immature and mature dendritic cells

Immature: principal function is antigen capture (is constantly sampling); there is expression of Fc receptors and mannose receptors; expression of molecules involved in T cell activation is low

Mature: principal function is antigen presentation to T cells; downregulates its ability to take up antigen so it doesn't waste energy sampling when it needs to present its antigen; high expression of molecules involved in T cell activation


Dendritic cells vs. B cells as antigen presenting cells

DCs effectively deliver both signals needed to activate T cells; they are the most efficient APC to function in the primary immune response

B cells that are specific for a given Ag are rare in primary response, but dramatically expand in secondary response; they are therefore efficient as APC in the secondary


Describe antigen uptake into endocytic components

Antigen is taken up from the extracellular space into intracellular vesicles → in early endosomes of neutral pH, endosomal proteases are inactive → acidification of vesicles activates proteases to degrade antigen into peptide fragments → vesicles containing peptides fuses w/ vesicles conaining MHC class II molecules


If antigen is brought into cell by antibody (antibody mediated uptake), what happens to the antibody?

Antibody gets effectively recycled to cell surface while antigen goes into meet w/ MHC class II


Describe antigen processing for exogenous (extracellular) antigens

Uptake of extracellular proteins into vesicular compartments of APC → processing of internalized proteins in endosomal/lysosomal vesicles

Meanwhile, MHC class II molecules synthesized in ER → has invariant chain blocking MHC binding site so antigen can't bind yet and also transmembrane region that aids in transport → transport through Golgi → ends up in "MHC class II compartment" → endosomal enzymes destroy the invariant chain except for CLIP peptide guarding MHC groove → fuses w/ vesicle containing antigen peptide → CLIP peptide release is catalyzed by HLA-DM → allows antigen peptide to bind to MHC class II molecule → expression of peptide-MHC complexes on cell surface


What are endogenously expressed antigens (in the cytoplasm of the cell) presented to?

CD8+ cytotoxic T cells


What are endogenous antigens presented with?

MHC class I


What cells are targets for CTL?

Any cell that expresses MHC class I can be a target for CTL

This includes antigen presenting cells and basically any nucleated cell


Where does processing of endogenuos antigens occur?

In proteasome


What are some examples of endogenous antigens?

Self (but body won't have T cells that can respond to this self-antigen)


What causes upregulation of proteasome components?

IFN (type I and II) signaling



What do proteasomes do?

Makes peptides of varying sizes from proteins (that have been ubiquinated and thus targeted)
Some of these peptides will be appropriate for binding to MHC class I


In endogenous antigen processing, how do peptides get from cytosol to where the MHC class I molecules are?

TAP1 and TAP2 actively take peptide and transport it across the lumen and into the ER

This process requires ATP


Describe processing of antigen in the Class I pathway

Production of proteins in the cytosol → proteolytic degradation of proteins by proteasome → transport of peptides from cytosol to ER by TAP → assembly of peptide-class I complexes in ER (until MHC class I molecule has peptide, don't assemble the entire molecule w/ the Beta-2 microglobulin) → transport to Golgi → Surface expression of peptide-class I complexes


What prevents binding of Class I peptides to MHC class II in the ER (since these peptides are transported into the ER by TAP)?

MHC class II molecules have CLIP peptide blocking antigen binding site

CLIP is only removed when MHC class II molecules have moved into the endocytic ocmpartments


What determines the outcome of an antigen?

Route of entry


Why aren't self-antigens presented by MHC molecules recognized by T cells?

There are either no T cells that recognize self-antigen or there is an inability to respond


Immunodominant epitopes

Peptides that bind most avidly to MHC


What is the effector function of CD4+ T cells?

Macrophage activation: destruction of phagocytosed antigen

B cell antibody secretion: antibody binding to antigen


Cross-presentation by dendritic cells

DC can effectively take up antigen from outside (such as virus infected cells) and presented to CD8+ cells


How is cross-presentation by dendritic cells advantageous?

Because DC doesn't have to be infected and is therefore less susceptible to virus escape

If the only way a dendritic cell could get activated was to get infected, the virus would just have to mutate so it doesn't actually infect the cells → this way, even material taken up will be presented


Presentation of antigen by CD1

CD1 is a non-polymorphic MHC-like molecule that maps outside of the MHC region

Like MHC class I, associates w/ beta-2 microglobulin

Capable of presenting mycolic acid and lipoarabinomannan (lipid and glycolipid) from myobacteria to T cells; source of antigen is exogenous and requires processing


What does CD1 on APC such as dendritic cells and thymic cortical cells do?

Able to present certain antigens (e.g. cerebrosides) to a population of CD4 T cells that express NK markers (NKT cells) or to some conventional T cells

These cells make cytokines, which helps shape the immune repsonse


What are CD1 molecules similar to?

MHC class I molecules

Molecular structure is similar

Also expresses beta-2 microglobulin



Bind outside of the peptide-binding cleft

Binds to the outside of the molecule and bring T cell receptor and MHC class II molecule together w/o processing

Superantigens can turn on a lot of different cells; end up w/ a lot of cells getting activated

Some bacterial toxins can thus damage the immune response


How is antigen presentation relevant to clinical medicine?

Transplantation (organs, bone marrow, stem cells)
Cancer: can tumor antigens be presented?
Infectious disease: upregulation and downregulation of MHC class I