Antigen Processing, Presentation, and Recognition

Question 1

Where are antigenic peptides made?

Answer 1

Made in APCs from pathogenic proteins.

Question 2

Do alphabeta T cells recognize free antigens?

Answer 2

No, they recognize antigens on pAPCs.

Question 3

How are resting T cells activated?

Answer 3

Resting T cells must be activated by pAPCs by receiving two signals.

Question 4

Which cells are pAPC’s?

Answer 4

Dendritic cells (most official), macrophages, and B Cells. These are the only cells that express both MHC class I and II.

Question 5

What happens when dendritic cells encounter pathogens in tissues?

Answer 5

The pathogens are entocytosed and processed into antigens. This causes pro inflammatory cytokine release in tissues, and the activation of chemokines that stimulate dendritic cell migration to lymphoid organs. Here, the DC presents the peptide to naive T cells.

Question 6

Gigantic diversity in MHC molecules results from…

Answer 6

Number of different genes, and variety of alternate forms of each gene. This is why transplant is so difficult. T Cells will only recognize self-MHC’s.

Question 7

Class I MHC Structure

Answer 7

Heterodimer of alpha and beta chains. Alpha chain is long and includes peptide binding cleft. Beta chain is short. Polymorphism of class I MHC is due to alpha chain.

Question 8

Class II MHC Structure

Answer 8

Heterodimer of alpha and beta chains, but the peptide binding cleft is made at the junction of the two chains (as opposed to just the alpha chain in class I).

Question 9

Where and how are MHC genes coded?

Answer 9

On chromosome 6. There are 3 different types of class I MHC (ABC), 3 different types of class II (DP, DQ, DR). We inherit 3 class I and 3 class II from each parent. All 12 are expressed on cell surface. There are over 1500 variations in each of the different types.

Question 10

HLA Class I Function

Answer 10

Binds 8-10aa’s, expressed on almost all nucleated cells. Presents cytosolic peptides to CD8+ T Cells to kill infected cells.

Question 11

HLA Class II Function

Answer 11

Binds 13-25 aa peptides. Expressed only on pAPCs and activated T cells. Presents external peptides to CD4+ T Cells to activate them.

Question 12

How do peptides bind to MHC?

Answer 12

Via anchor residues. MHC alleles at the various loci differ in their anchor residues. For example, HLA A1 has anchor residues at position 5 and 8, but HLA A2 has anchor residues at 2 and 9.

Question 13

How do T cell receptors recognize the MHC/peptide complex?

Answer 13

Have binding clefts for the MHC and the peptide.

Question 14

Why is variability in the MHC important?

Answer 14

MHC molecules need to be able to bind peptides from all pathogens. So most of the molecule is constant, but the peptide binding cleft is extremely polymorphic.

Question 15

Can MHC bind different peptides?

Answer 15

Not at once, but can definitely bind different peptides at different times.

Question 16

Is the binding of a peptide to MHC short or long lived?

Answer 16

Relatively long lived and stable to give the T cell time to read it.

Question 17

What are the two major pathways by which APCs process pathogens?

Answer 17

Exogenous and Endogenous pathways

Question 18

Exogenous pathway

Answer 18

For antigens that come from outside the cell (ie. bacteria). Antigen is taken into vesicular compartments within the APC and are broken down into peptides in the lysosome. Meanwhile, class II MHCs are being assembled in the ER: alpha and beta chains are being put together, but their binding site is blocked by the invariant chain. The complex passes through the golgi and meets up with the endosome, where HLA DM chews invariant chain to let peptide bind. MHC II + Peptide transported to cell surface for presentation to CD4 cells.

Question 19

Endogenous pathway

Answer 19

For antigens from pathogens that replicate within cell (viruses). First, when viral proteins are produced in the cytosol, they are ubiquitinated and degraded into peptides by the proteasome. The peptides make their way to the ER, where TAP transports them across. Here, open class I MHCs are waiting. When the peptide binds, the MHC is stabilized, sent through the Golgi and presented to activated CD8+ T cells on the surface.

Question 20

Cross Presentation

Answer 20

A third antigen presentation mechanism where infected cells are picked up by APCs, expressed with MHC class I and stimulate naive CD8+ CTL activated without being infected themselves. Generally in Dendritic Cells.

Question 21

Where and when are B and T cell receptors developed?

Answer 21

In lymphoid organs, before exposure to antigens. Think about the department store analogy, an antigen walks into a department store, the suit that is already perfectly tailored to it is put on, then the department store makes many more of those suits, anticipating demand.

Question 22

What are B cell receptors? What do they bind to?

Answer 22

Membrane-bound antibodies. They bind to macromolecules and conformational/linear epitopes.

Question 23

Antibody Structure

Answer 23

Two heavy and two light chains. Fc region at the bottom a product of the heavy chains only, determines function of the antibody. Antigen binding site made of variable regions of the heavy and light chains. Also, two types of light chains exist, but are never mixed on the same immunoglobulin.

Question 24

CDRs

Answer 24

Complementary Determining Regions. Each V-domain has 3 hypervariable regions (created from 3 CDRs in Vh and 3 CDRs in VL, or alpha/beta). These act like fingers that interact with antigens.

Question 25

T Cell Receptor Structure

Answer 25

Two chains, alpha and beta. One variable domain, one constant region. Binds to peptides presented by MHC.

Question 26

Process of T and B Cell Maturation

Answer 26

Pre-B/T cells must express one chain of their antigen receptor before proliferation, otherwise death. Then receptor is completed and tested against self antigens. Strong reactivity leads to death, weak reactivity leads to maturation.

Question 27

What two genetic processes increase diversity of TCRs and Ig’s?

Answer 27

Germ line configuration rearranges genes. Somatic recombination generates incredible diversity.

Question 28

Somatic Recombination in B Cells

Answer 28

Process occurs in heavy chains first. D and J regions join. There any many forms of these. Then, The DJ region recombines with any one of the many V regions. Then if this is successful, this occurs in light chains (but only V and J, no D region exists). If both are successful, other chromosome recombination is prevented.

Question 29

What happens if recombined gene segments from somatic recombination in B cells don’t line up properly?

Answer 29

The gaps are filled by Terminal Deoxyribonucleotidyl Transferase (TDT). Sometimes, nucleotides can be gained or lost too, creating increased diversity.

Question 30

Can there ever be changes in constant regions of Igs or TCRs?

Answer 30

In Igs, yes. This is called class switching. This does not occur in TCRs.

Question 31

Creation of monoclonal antibodies

Answer 31

Inject antigen X into mouse. Fuse the spleen B cells (some including anti-X antibody) to a tumor to cause unlimited proliferation. Isolate the antibody and humanize.

Question 32

T Cell maturation

Answer 32

A pre-T cell has either CD4 or CD8 but then has both. When the TCR binds to an MHC, whichever class determines which coreceptor remains.

Question 33

Death by neglect

Answer 33

When T cells mature, this occurs if there is no recognition of MHC and peptide.

Question 34

Can any heavy chain associate with any light chain?

Answer 34

Yes