Immunology (BIOL 318) Lectures 10 + 11

Antigen presentation and MHC

_____ can only detect antigens presented to them, as opposed to _____, which can also detect free antigens

T cells; B cells

CD4⁺ T cells recognize ________ antigens, while CD8⁺ T cells recognize ________ antigens

Exogenous; endogenous

Under what conditions and antibodies bind to antigens?

• Intact

• On the surface of microbes or infected host cells

• Free, without being presented by MHC

Do antibodies bind the entire antibody or just an epitope?

Epitope

Characteristics of antigens recognized by T cells

• Linear and small peptide from the antigen

• Cell-associated antigens

• Presented by APCs

T cells recognize antigens in…

The lymph nodes

Costimulators

Molecules that assist in the activation of naive T cells to effector T cells

B7 family of costimulators

• Ligands expressed on the surface of APCs that bind to receptors on naive T cells

• Responsible for “step 2” of T cell activation

APCs include…

Dendritic cells, macrophages, and B cells

What is “step 1” of T cell activation?

Antigen recognition, which occurs when the TCR of a naive T cell binds to an antigen presented by MHC

B7-1 (CD80)

• Constimulator on APC surface

• Binds to CD28 on T cell surface

B7-2 (CD86)

• Costimulator on APC surface

• Binds to CTLA-4 on T cell surface

B7-H1 (PDL1)

• Costimulator on APC surface

• Binds to PD1 on T cell surface

Costimulator and MHC II expression in APCs is increased by…

• IFN-γ

• IL-4

• CD40-CD40L interaction

CD40-CD40L interaction effect

• Activates APCs to express more costimulators and cytokines

• CD40L is a ligand on activate T cells, which binds to CD40 (a receptor) on APCs

Expression of MHC II in dendritic cells is increased by…

• IFN-γ

• Signals from TLRs

Expression of MHC II in macrophages is increased by…

• IFN-γ

Expression of MHC II in B cells is increased by…

• IL-4

• Antigen receptor cross-linking

Expression of costimulators in dendritic cells is increased by…

• CD40-CD40L interaction

• IFN-γ

Expression of costimulators in macrophages is increased by…

• CD40-CD40L interaction

• IFN-γ

Expression of costimulators in B cells is increased by…

• CD40-CD40L interaction

• Antigen receptor cross-linking

Goal of tissue-resident dendritic cell

• Endocytose microbes

• Process internalized antigens to be presented on MHC

Goal of activated dendritic cell

• Migrate to lymph nodes

• Present antigens to T cells using MHC

CCR7

• GPCR on dendritic cells and T cells

• Binds to CCL19 & CCL21 (chemokines)

• Stimulates migration to lymph nodes

• Stimulates higher expression of MHC II and costimulators in dendritic cells

cDC1s are a type of specialized dentritic cell (conventional dendritic cell 1) that coross presents specifically to…

Naive CD8+ T cells

_____ activate macrophages

Th1 cells (a subset of CD4+ T cells)

What happens when a macrophage is activated by a helpter T cell?

It kills the microbes that it has already ingested prior

T-cell dependent antibody production

• B cells internalize antigens + present peptides derived from them to helper T cells

Where do memory B cells loiter?

• Spleen

• Bone marrow

• A small amount can be found in tissues

What type of antibody is this? (Hint: looks similar to some others, but this is the most abundant in the plasma out of those)

IgG

What type of antibody is this?

IgM

What type of antibody is this?

IgA

MHC class I molecules in humans are encoded by:

HLA-A, HLA-B, HLA-C

MHC class I molecules in humans include:

HLA-DP, HLA-DQ, HLA-DR

The structure of HLA is similar to…

Immunolglobulins

Which class of MHC can bind to a more diverse set of epitopes, and why?

• MHC II

• The peptide binding cleft is composed of two separate pieces, whle MHC I has a peptide binding cleft composed of one continuous piece

MHC I has ___ transmembrane region(s)

One

MHC II has ___ transmembrane region(s)

Two

MHC I is expressed by…

All nucleated cells

MHC II is expressed by…

APCs and thymic epithelial cells

The MHC locus is located on chromosome…

6p

Viral proteins are chopped up into smaller peptides by ____ in the _____ (MHC I expression)

Proteosomes; cytoplasm

Viral/pathogenic peptides enter the _____ through ______ (MHC I expression)

ER; TAP (Transorter associated with Antigen Processing)

Viral/pathogenic peptides are bound to MHC I in the ___ before being transported to the ____

ER; Golgi

The MHC I antigen complex is transported from the Golgi to the _______ in an ________

Plasma membrane; exocytic vesicle

Internalized proteins are processed in _________ (MHC II expression)

Endosomal/lysosomal vesicles

MHC II is synthesized in the _____ before being transported to the ____

ER; Golgi

The processed peptides bind to MHC II in ______ before being expressed on the cell surface

Lysosomes

Positive selection of T cell location

Cortex (edge) of the thalamus

Negative selection of T cell location

Medulla (middle) of the thymus

CCR9

• Receptor expressed by newly synthesized T cells

• Interacts with CCL25 (expressed in thymus)

• Causes T cells to migrate to the thymus

After positive and negative selection in the thymus, _____ expression on T cells in downregulated

CCR9