Lecture 5: Antigen Capture and Presentation

Question 1

What are APCs

Answer 1

• antigen presenting cells
• capture Ags in tissues and transport these Ags to peripheral lymphoid tissues where lymphocytes are concentrated, to present them to T cell

Question 2

What do intracellular pathogens activated by

Answer 2

MHC-I

Question 3

What are extracellular activated by

Answer 3

MHC-II

Question 4

What are co-stimulatory molecules

Answer 4

• act as a second signal for T cell activation
• up-regulated by PRR
• warns T-cells of danger

Question 5

What is the MHC locus

Answer 5

• originally discovered as principle determinant of graft rejection. people with the same MHC accept grafts, while people with different MHCs reject MHCs
• collection of genes found in all mammals that code for MHC molecules; two sets of highly polymorphic genes

Question 6

What is polymorphism

Answer 6

multiple alleles of a gene within a population

Question 7

What are properties of MHC-peptide interactions (4 points)

Answer 7

• binding clefts have pockets
• antigenic peptides fit into pockets and anchor peptide into MHC peptide-binding cleft
• 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

Question 8

What are class II MHC-expressing cell types

Answer 8

• professional APCs, macrophages, B cells
• CD4+ helper lymphocytes interact with dendritic cells, macrophages, B lymphocytes

Question 9

What are class I MHC-expressing cell types

Answer 9

CD8+ CTLs can kill any virus-infected cell

Question 10

What are class I MHCs

Answer 10

• an alpha chain, noncovalently linked to a beta2-microglobulin chain

Question 11

What are features of class I MHCs (4 points)

Answer 11

• alpha1 and alpha2 form a peptide binding groove that holds peptides of 8-11 amino acids
• 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
• polymorphic residues are located in the alpha1 and alpha2 domains of Class I MHC molecules, thereby affecting peptide binding and T cell recognition
• the alpha3 domain is invariant and contacts the T cell CD8 co-receptor. Thus, only CD8+ T lymphocytes respond to class I MHC bound antigens

Question 12

What is the process of converting microbial proteins into peptides for MHC Class I (7 steps)

Answer 12

1. Microbes grow and reproduce in cytoplasm producing their microbial proteins
2. Results in microbial proteins in the cytoplasm of infected cells
3. Proteins are cleaved into peptides of varying sizes 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

Question 13

What are some features of the class I pathways

Answer 13

• responds to intracellular microbes
• intracellular microbes are presented by Class I MHC molecules on the surface of all nucleated cells
• Class I MHC - peptide complexes are recognized by CD8+ T lymphocytes
• TCR activation triggers T lymphocyte differentiation to cytotoxic T lymphocytes (CTL). CTLs kill target infected cells, thereby eradicating the infection

Question 14

What are class II MHCs (5 points)

Answer 14

• an alpha chain, noncovalently linked to a beta chain
• alpha1 and beta1 domains form a peptide binding groove that holds peptides of 10-30 amino acids
• TCR contacts residues of the antigenic peptide that extend up out of the peptide binding groove
• polymorphic residues of class II MHC are in the alpha1 and beta1 domains, affecting peptide binding and T cell recognition
• beta2 domain is invariant and contacts the T cell CD4 co-receptor. thus, only CD4+ T lymphocytes respond to Class II MHC-bound antigens

Question 15

What is the process of converting microbial proteins into peptides for MHC class II (7 steps)

Answer 15

1. APCs have several means of ingesting microbes
   a) PRR binds 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 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

Question 16

What are some features of the class II pathway

Answer 16

• microbes are captured by APCs, B lymphocytes and phagocytes
• microbial antigens are presented by class II MHC
• class II MHC - peptide complexes are recognized by CD4+ T lymphocytes
• 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

Question 17

What is co-dominance

Answer 17

• 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

Question 18

What is polymorphism

Answer 18

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

Question 19

What is a very slow off rate?

Answer 19

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

Question 20

What is stable expression requires peptide

Answer 20

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

Question 21

Why do MHC molecules only bind peptides

Answer 21

MHC restricted T cels respond only to protein antigens, and not to other chemicals

Question 22

What are co-stimulatory functions of APCs

Answer 22

• present antigens and provide the second signal for T cell activation
• present microbial peptides via Class II MHC molecules