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IMIN 200 > Lecture 5: Antigen Capture and Presentation > Flashcards

Lecture 5: Antigen Capture and Presentation Flashcards

1
Q

Lymphocytes constantly recirculate between tissues to kill microbes. What are the steps on how they do this?

A
  1. Lymphocytes enter lymph nodes, where they encounter APCs.
  2. Lymphocytes are activated and differentiate in the lymph nodes.
  3. Lymphocytes exit lymph nodes and enter circulation, head to inflamed tissues where they mediate microbial destruction.
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2
Q

What activates the T cells?

A

Antigen Presenting Cells (APC)

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3
Q

How does the antigen presenting cells (APC) activate T cells?

A

APCs capture antigens (Ags) in tissues and transport these Ags to peripheral lymphoid tissues (lymph nodes usually) where lymphocytes are concentrated, to present those Ags to T cells.

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4
Q

Major Histocompatibility Complex (MHC) class I and II molecules

A

APC present peptide antigens to T cells on MHC class I and class II molecules

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5
Q

These antigens are linear peptides bound and presented by MHC molecules

A

T cell antigens

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6
Q

MHC locus

A
  • collection of genes found in all mammals that code for MHC molecules. The locus contains two sets of highly polymorphic genes (Class I and Class II)
  • originally discovered as principle determinant of graft rejection.
  • people with the same MHCs (e.g. twins) accept grafts.
  • people with different MHCs reject grafts.
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7
Q

Polymorphism

A

multiple alleles of a gene within a population

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8
Q

What does the Class I and Class II genes code for?

A

Class I and Class II genes code for the Class I and Class II molecules that display peptides to T cells

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9
Q

Most MHC peptide binding clefts have ______

A

pockets

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10
Q

What fits into the MHC pockets of MHC binding clefts and what do they do?

A

Side chains of two or three amino acids of antigenic peptides fit into the MHC pockets and “anchor” the peptide in the MHC peptide-binding cleft.

Additional amino acid residues of the antigenic peptide extend upwards and are recognized by TCR.

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11
Q

Why does MHC molecules have a broad specificity?

A
  • any given MHC can present any peptide with the correct anchor residues.
  • Thus, MHC molecules have a broad specificity, allowing a small number of MHC molecules to display a large array of peptide antigens.
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12
Q

What happens to when peptides are bound to the MHC?

A

When bound, peptides remain on display for up to days maximizing the likelihood of encountering the correct T cell.

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13
Q

What are the MHC-expressing cell types of Class II MHC molecules?

A
  • dendritic cell
  • macrophage
  • B cell
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14
Q

What are the MHC-expressing cell types of Class I MHC molecules?

A

All nucleated cells

  • leukocytes
  • epithelial cells
  • mesenchymal cells
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15
Q

CD4+ helper T lymphocytes

A

interact with dendritic cells, macrophages, B lymphocytes

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16
Q

CD8+ CTLs

A

can kill any virus-infected cell

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17
Q

Structure of Class I MHC
What is it made of?

A
  • an α chain, noncovalently linked to a β2-microglobulin chain.
  • α1 and α2 domains form a peptide binding groove that holds peptides of 8-11 amino acids.

-TCR on top of the MHC molecule

  • Polymorphic residues located in the α1 and α2 domains of Class I MHC molecules
  • α3 domain
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18
Q

Where does the TCR stay on the Class I MHC molecule and what does it do?

A

The TCR sits down on the top of the MHC molecule and contacts residues extending up out of the peptide binding groove on the antigenic peptide.

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19
Q

Where are polymorphic residues located in the Class I and II MHC molecule?

A

Polymorphic residues are located in the α1 and α2 domains of Class I MHC molecules, thereby affecting peptide binding and T cell recognition.

20
Q

α3 domain of Class I MHC molecule

A

The α3 domain is invariant and contacts the T cell CD8 co-receptor. Thus, only CD8+ T lymphocytes (cytotoxic T cells) respond to Class I MHC-bound antigens.

21
Q

Antigen Processing- Converting microbial proteins into peptides for the MHC

Steps (Class I)

A
  1. Microbes (viruses, bacteria) grow and reproduce in the cytoplasm producing their microbial proteins.
  2. This results in microbial proteins in the cytoplasm of infected cells.
  3. Proteins are cleaved into peptides of varying size and composition by the cytoplasmic proteasome complex.
  4. Newly synthesized Class I MHC molecules are loosely attached to the Transporter associated with Antigen Presentation (TAP), a cellular pump that drives transport of cytoplasmic peptides into the E.R.
  5. Microbial peptides are pumped into the E.R. lumen by TAP, where they associate with Class I MHC molecules.
  6. If a Class I molecule stably binds a microbial peptide, the complex is sent to the cell surface, via the Golgi apparatus and exocytic vesicles.
  7. Class I MHC- peptide complexes are delivered to the cell surface where they interact with CD8+T lymphocytes.
22
Q

The Class I pathway responds to ___________ microbes

A

intracellular

23
Q

Intracellular microbes are presented by Class I MHC molecules on the _______________

A

surface of all nucleated cells

24
Q

Class I MHC- peptide complexes are recognized by _____________

A

CD8+ T lymphocytes

25
Q

Class I MHC-peptide complexes are recognized by CD8+ T lymphocytes. What happens when TCR is activated?

A

TCR activation triggers T lymphocyte differentiation to cytotoxic T lymphocytes (CTL). CTLs kill target infected cells, thereby eradicating the infection.

26
Q

Class II MHC molecule structure

What is it made of?

A
  • an α chain, noncovalently linked to a β chain.
  • α1 and β1 domains form a peptide binding groove that holds peptides of 10-30 amino acids.
  • polymorphic residues of Class II MHC are in the α1 and β1 domains, affecting peptide binding and T cell recognition.
  • β2 domain
27
Q

β2 domain of Class II MHC molecules

A
  • β2 domain is invariant and contacts the T cell CD4 co-receptor. Thus, only CD4+ T lymphocytes (helper T cells) respond to Class II MHC-bound antigens.
28
Q

What does the TCR does in the MHC II molecules?

A

The TCR contacts residues of the antigenic peptide that extend up out of the peptide binding groove.

29
Q

Antigen Processing- Converting microbial proteins into peptides for the MHC

Class II Steps

A
  1. APCs have several means of ingesting microbes
    a. PRR bind microbes
    b. Receptors bind antibodies bound to microbes
    c. APCs sample their environment through pinocytosis
  2. Internalized microbes are delivered to lysosomes
  3. Microbial proteins are cleaved by lysosomal enzymes, yielding numerous microbial peptides of different sizes and configuration
  4. In the ER, a protein called the invariant chain, blocks the peptide binding groove of MHC II, preventing peptides associating with MHC II in the ER.
  5. Class II molecules are transported to the cell surface in exocytic vesicles.
  6. Endosomal vesicles with microbial peptides fuse with exocytic vesicles containing MHC II molecules. Invariant chain is degraded and MHC II binds microbial peptides.
  7. If MHC II stably binds a microbial peptide the complex is transported to the cell surface
30
Q

What are the several means that APCs ingest microbes (Class II)

A
  • PRR bind microbes
  • Receptors bind antibodies bound to microbes
  • APCs sample their environment through pinocytosis
31
Q

The Class II pathway responds to __________ microbes

A

extracellular

32
Q

In the Class II pathway, microbes are captures by ________, __________, and __________.

A

APCs, B lymphocytes, and phagocytes

33
Q

In class II pathway, microbial antigens are presented by _____________

A

Class II MHC

34
Q

Class II MHC-peptide complexes are recognized by ____________.

A

CD4+ T lymphocytes

35
Q

What happens when CD4+ T lymphocytes stimulate B lymphocytes?

A

CD4+ T lymphocytes stimulate B lymphocytes to produce antibodies and phagocytes to ingest and destroy microbes. These pathways are most suited for the destruction of extracellular microbes.

36
Q

Two properties of the MHC

A
  • Co-dominance
  • Polymorphism
37
Q

Co-dominance

A

Property of MHC

Both parental alleles are expressed equally. This means that each individual can express up to 6 different Class I molecules and 10 to 20 different Class II molecules.

38
Q

Polymorphism

A

Property of MHC

Multiple MHC alleles means that at least some members of the population will be able to present any given microbial antigen.

39
Q

features of peptide binding to MHC

A
  1. Each MHC molecule displays one peptide at a time
  2. Broad specificity
  3. Very slow off-rate
  4. Stable expression requires peptide
  5. MHC molecules bind only peptides
40
Q

What is the significance of each MHC molecule displaying one peptide at a time?

A

Each T cell responds to a single peptide bound to an MHC molecule

41
Q

What is the significance of peptide binding to MHC molecules having broad specificity?

A

Many different peptides can bind to the same MHC molecule

42
Q

One feature of peptide binding to MHC is it has very slow off-rate. What is the significance of this?

A

MHC molecule displays bound peptide for long enough to be located by T cell.

43
Q

One feature of peptide binding to MHC is stable expression requires peptide. What is the significance?

A

Only MHC molecules that are displaying peptides are expressed for recognition by T cells

44
Q

One feature of peptide binding MHC is MHC molecules bind only peptides. What is the significance?

A

MHC-restricted T cells respond only to protein antigens, and not to other chemicals.

45
Q

Co-stimulatory functions of APCs

A
  • APCs present antigens and provide the second signal for T cell activation.
  • APCs present microbial peptides via Class II MHC molecules.
  • CD4+ T lymphocytes recognize Class II MHC-peptide complexes.
  • Microbial substances stimulate APCs to express costimulators on their surface and secrete cytokines.
  • Costimulators and cytokines provide the second signal that triggers T lymphocyte differentiation.

IMIN 200 (20 decks)

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