Lecture 4: Antigen Capture and Presentation to Lymphocytes

What complex does a T cell receptor (TCR) recognize?

A complex of peptide antigen displayed by an MHC molecule.

According to Figure 4-4, what can antibodies accommodate in their antigen-binding site?

Soluble macromolecules in their native (folded) conformation.

In the model of Figure 4-4, what color represent the heavy chains of the antibody?

Red.

In the model of Figure 4-4, what color represent the light chains of the antibody?

Yellow.

In the model of Figure 4-4, what color represent the antigens?

Blue.

What laboratory provided the model for Figure 4-4?

Cold Spring Harbor Laboratory.

Which specific polysaccharide is mentioned as a recognition target for antibodies?

O-antigens.

Besides proteins and polysaccharides, name three types of molecules antibodies can recognize.

Lipids, nucleic acids, and small molecules.

What is the name of the small molecule mentioned as antigenic for antibody recognition?

Digoxigenin.

Through which vessel do Naive T cells enter a lymph node?

High endothelial venule (HEV).

Where do effector or memory T cells migrate after leaving the blood vessel?

Peripheral tissue.

What vessel do lymphocytes use to exit a lymph node?

Efferent lymphatic vessel.

Name the three types of Antigen Presenting Cells (APCs) shown in Figure 1-18.

Dendritic cell, Macrophage, and B cell.

What are the two outcomes of naive T cell activation?

Clonal expansion and differentiation into effector T cells.

What receptor on a Naive T cell binds to the costimulator (e.g., B7)?

$$CD28$$

Activation of macrophages by effector T cells is an example of what kind of immunity?

Cell-mediated immunity.

B cell activation and antibody production by effector T cells is an example of what kind of immunity?

Humoral immunity.

What is the primary function of cytotoxic T cells (CTLs)?

Killing of infected cells with microbes in the cytoplasm.

Where are immature dendritic cells typically found?

In tissues.

Where are mature dendritic cells found within lymph nodes?

In T-cell rich areas.

What is the primary role of dendritic cells in the immune system?

Antigen capture and presentation.

What are required for antigen presentation by dendritic cells to activate naive T cells?

Costimulators.

Which molecules are expressed on APCs to display peptides derived from protein antigens?

Major histocompatibility complex (MHC) molecules.

How do peptides bind to MHC molecules?

By anchor residues that attach to pockets in the MHC molecules.

A T cell receptor recognizes which two components of the MHC-peptide complex?

Residues of the peptide and polymorphic residues of the MHC molecule.

In humans, what is the Major Histocompatibility Complex (MHC) called?

HLA (Human Leukocyte Antigen).

Which loci make up the Class II MHC in humans?

DP, DQ, and DR.

Which loci make up the Class I MHC in humans?

B, C, and A.

What is the MHC called in mice?

H-2

Which loci make up the Class II MHC in mice?

I-A and I-E.

Which loci make up the Class I MHC in mice?

K, D, and L.

Which genes are located within the Class II MHC locus according to the diagram?

DM, Proteasome genes, TAP1, and TAP2.

Name three complement proteins found within the MHC locus.

C4, Factor B, and C2.

Name three cytokines found within the MHC locus.

LTB, TNF-$\alpha$, and LT.

Which regions of the Class I MHC molecule are polymorphic?

$\alpha 1$ and $\alpha 2$

To which part of the Class I MHC molecule does the CD8 T cell co-receptor bind?

$$\alpha 3$$

CD8+ T cells can only respond to antigen presented by which class of MHC?

MHC class I.

CD4+ T cells can only respond to antigen presented by which class of MHC?

MHC class II.

What is the size range of peptides that fit in the Class I MHC peptide-binding cleft?

$8-9$ amino acids.

Which regions of the Class II MHC molecule are polymorphic?

$\alpha 1$ and $\beta 1$

To which parts of the Class II MHC molecule does the CD4 T cell co-receptor bind?

$\alpha 2$ and $\beta 2$

What is the size range of peptides that fit in the Class II MHC peptide-binding cleft?

$10-30$ amino acids.

Which genes in the genome are described as the most polymorphic?

Class I and class II MHC genes.

Approximately how many HLA class I alleles are estimated in the human population?

$$10,000$$

Approximately how many HLA class II alleles are estimated in the human population?

$$3,000$$

How are MHC alleles inherited and expressed from parents?

Codominant expression.

What does 'broad specificity' mean in the context of MHC molecules?

Many different peptides can bind to the same MHC molecule.

How many peptides can an MHC molecule display at a single time?

$$1$$

MHC molecules bind only to which type of biological molecule?

Peptides (Proteins).

MHC molecules do not bind to which types of molecules according to Figure 3-1?

Lipids, carbohydrate sugars, and nucleic acids.

Where are peptides acquired for Class I MHC molecules?

During intracellular assembly in the ER (cytosolic peptides).

Where are peptides acquired for Class II MHC molecules?

In endocytic vesicles.

What is required for the stable surface expression of an MHC molecule?

A bound peptide.

What happens to 'empty' MHC molecules regarding surface expression?

They are not expressed on the cell surface.

What is the significance of the very slow off-rate for MHC-peptide binding?

The MHC molecule displays the peptide long enough to be located by a T cell (measured in days).

Which pathway processes cytosolic antigens?

Class I MHC pathway.

Which pathway processes internalized vesicular antigens?

Class II MHC pathway.

Which cells recognize endogenous antigens presented by MHC Class I?

CD8+ Cytotoxic T cells (CTLs).

Which cells recognize exogenous antigens presented by MHC Class II?

CD4+ Helper T cells.

What is cross-presentation?

A process where host APCs pick up viral antigens from infected cells and present them to CD8+ T cells via Class I MHC.

Which cell type is primarily responsible for cross-presentation?

Dendritic cell.

In the Class I MHC pathway, antigens are typically synthesized where?

In the cytosol (e.g., viral proteins).

In the Class II MHC pathway, antigens are typically obtained from where?

The extracellular environment (extracellular microbes).

What type of T cell provides signals for macrophage activation?

CD4+ helper T lymphocyte.

What type of T cell helps B cells secrete antibodies?

CD4+ helper T lymphocyte.

What is the functional result of CD8+ T cell recognition of an antigen-expressing target cell?

Killing of the target cell.

What is the significance of MHC-restricted T cells?

They respond mainly to protein antigens.

What is the role of $TAP1,2$ in the MHC locus?

Transporting peptides into the ER for MHC Class I assembly.

Which MHC class contains the $\beta 2$-microglobulin component?

Class I MHC.

What are 'professional' APCs?

Cells specialized in capturing and presenting antigens to T cells, such as Dendritic cells, Macrophages, and B cells.

Where is the MHC locus located in the human genome?

HLA complex.

Is Class II MHC DP polymorphic?

Yes, it is part of the polymorphic Human HLA locus.

Is Class II MHC DQ polymorphic?

Yes, it is part of the polymorphic Human HLA locus.

Is Class II MHC DR polymorphic?

Yes, it is part of the polymorphic Human HLA locus.

Which T cell co-receptor binds to the non-polymorphic region of MHC Class II?

$$CD4$$

Which T cell co-receptor binds to the non-polymorphic region of MHC Class I?

$$CD8$$

In the mouse H-2 locus, what is the Class I equivalent to human HLA-A/B/C?

K, D, and L.

In the mouse H-2 locus, what is the Class II equivalent to human HLA-DP/DQ/DR?

I-A and I-E.

Which pathway uses the proteasome for antigen processing?

Class I MHC pathway.

What is the source of peptides for MHC class I molecules?

Cytosolic proteins/antigens.

What is the source of peptides for MHC class II molecules?

Internalized vesicular (extracellular) antigens.

Which MHC class involves peptides transport into the Endoplasmic Reticulum (ER)?

Class I MHC.

Which MHC class involves peptides entering from endocytic vesicles?

Class II MHC.

What does a dendritic cell do with fragments of virally infected cells in cross-presentation?

It picks them up and presents them via its own Class I MHC.

What is the consequence of lack of MHC polymorphism in a population?

Inability to bind diverse peptides, limiting immune responses.

Which MHC class is restricted to CD4+ T cell responses?

MHC Class II.

Which MHC class is restricted to CD8+ T cell responses?

MHC Class I.

Which APC type is associated with humoral immunity?

B cell.

Which APC type is associated with killing of phagocytosed microbes via macrophage activation?

Macrophage.

Where do dendritic cells mature?

As they migrate from tissues to T-cell rich areas in lymph nodes.

What name is given to the T cell that has not yet encountered an antigen?

Naive T cell.

What molecule on the APC surface is B7?

A costimulator.

Does an antibody recognize antigens in their denatured or native state?

Native (folded) conformation.

What type of molecules are O-antigens?

Polysaccharides.

According to Figure 1-18, what provides the blood supply to the lymph node?

Artery.

According to the transcript, macrophages and B lymphocytes are also important what?

Important APCs.

What allows a single MHC molecule to bind many different peptides?

Broad specificity.

How long is the off-rate for MHC-bound peptides typically measured?

In days.

Where is the peptide-binding cleft located on an MHC Class I molecule?

Between the $\alpha 1$ and $\alpha 2$ domains.

Where is the peptide-binding cleft located on an MHC Class II molecule?

Between the $\alpha 1$ and $\beta 1$ domains.