Antigen Capture and Presentation

Question 1

How does the innate immune response innate the adaptive immune response?

Answer 1

1. process and present antigen to T lymphocytes

2. Generation of surface molecules that function as costimulatory signals with antigen to active T and B lymphocytes

Question 2

What are MHC/HLAs?

Answer 2

Antigen presenting molecules that allow immune system to distinguish between self and non-self.

Germline encoded, two halotypes from parents that are co-dominate allowing for more diversity

Question 3

What are general structural features of Class I MHC/HLA?

Answer 3

Heterodimer of 2 proteins

Class I genes encoded by 3 seperate gene regions (A, B, and C)

• alpha chain encoded by MHC/HLA class locus, forms 3 domains (alpha 1, 2, and 3), membrane bound glycoprotein
• Beta2 micoglbulin, non MHC encoded, associates non covalently with the alpha 3
• peptide bond between alpha 1 and 2 (area of variability)

Closed ends in peptide binding groove= size limit

All alleles of Class I can expressed at the same time of each cell

Question 4

What is the role of Class I MHC/HLAs?

Answer 4

Present CD8 cytotoxic T

Inhibitory receptor for NK Cells

Question 5

What are the general structural feature of Class II MHC/HLA?

Answer 5

Encoded by HLA-D region

two proteins= alpha and b chain that are strongly associated via peptide forming binding groove NOT covalently linked

four globular domain structure just like class one

Open ends allow larger peptides to bind

All alleles of the alpha and beta expressed (3 alpha and 3 beta from mom and 3 alpha and beta from dad), can associate however they want –> diversity

Question 6

What is the role of Class II MHC?

Answer 6

Presents antigen to CD4+ T

Question 7

Where do you find Class I MHC?

Answer 7

All nucleated cells

Question 8

Where do you find Class II MHC?

Answer 8

antigen presenting cells= macrophages, dendritic, and B-lymphocytes

Question 9

What are the key features of HLA peptide binding?

Answer 9

Slow on rate and very slow off rate so can actually present antigen, saturable low affinity interaction

Only one peptide binds to a molecule at a time even though is able to bind multiple different ones (pockets specific for size, shape, and hydrophobicity, not AA sequence)

Question 10

How is MHC restricted?

Answer 10

CD4+ binds Class II MHC beta chain
CD8+ binds Class I MHC alpha 3 domain
everything equals 8

Question 11

What are the 3 main types of APCs?

Answer 11

Dendritic cells, macrophages, B lymphocytes

Question 12

What is the distinct cell marker expression, costimulators and function of Dendritic Cells?

Answer 12

Professional APCs because constitutive expression of MHC II, increased by IFN-gamma

Costimulators constitutive, increased by TLR ligands, IFN-gamma, and T cells

APC for native T cells

Question 13

What is the distinct cell marker expression, costimulators and function of macrophages?

Answer 13

low or negative expression of Class II MHC (inducible by IFN-gamma)

low expression of costimulators, induced by IFN-gamma, TLR ligands, and T cells, get from NKs

APC for CD4+ effector T cells

Question 14

What is the distinct cell marker expression, costimulators and function of B lymphocytes?

Answer 14

Class II MHC constitutive, increased by cytokines (IL-4)

Costimulators induced by T cells and antigen receptor cross linking during immune synapse

APC for CD4+ helper T cells in humoral response

Question 15

What is the pathway of antigens captured in the periphery in comparison to the blood?

Answer 15

Periphery= filter by lymph and lymphoid tissues

Blood= filtered by spleen (macrophages)

Question 16

What happens when dendritic cells are activated?

Answer 16

Once activated lose adhesive markers and upregulate CCR7 for binding to lymph endothelium

Increase expression of MHC and CD80 (costim.)

Travel to lymph tissue and mature during migration before presenting antigen to naive T

Question 17

What is the Class II MHC pathway for processing?

Answer 17

Vesicle binds with lysosome in cell making peptides
At same time HLA alpha and beta chains being made in ER and held together by invariant chain which keeps peptide from binding the groove

The molecule goes to the golgi via exocytotic vesicle. binds with lysosome that has degraded peptides.

Lysosome enzymes degrade invariant leaving CLIP

HLA-DM exchanges CLIP for peptides for Class II MHC and displays on cell surface

Question 18

What is the Class I MHC pathway for processing?

Answer 18

Proteins produced in cytosol are degraded via proteasome

In interior of ER Class I alpha chain made, tapasin holds molecule there as TAP feeds peptides from cytosol into ER and complex assembled

Transported to the golgi and then exocytoced on to cell surface for CD8+ cytotoxic

Question 19

Why is CLIP so important?

Answer 19

MHC I protein complexes are being made at the same time in ER don’t want intra cellular thing presented to Class II

Question 20

What is cross presentation?

Answer 20

Permits the presentation of exogenous antigens, which are normally presented by MHC II on the surface of dendritic cells, to also be presented through the MHC I pathway
- use MHC 1 to remain unaffected and MHCII to signal adaptive immune response to T cells

Question 21

What is ankylosing spondylitis? What HLA allele is it associated with?

Answer 21

inflammation of the spine

HLA-B27

Question 22

What is Rheumatic fever? What HLA allele is associated with it

Answer 22

Generation of antibodies against strep that cross-react with cardiac tissue

HLA-DR4

Question 23

What is a cause of renal cell carcinoma?

Answer 23

Class I antigen processing defect= TAP (transporter) down regulated

Question 24

What causes Bare Lymphocyte Syndrome?

Answer 24

TAP protein non functional so peptides cannot enter the ER and bind to Class I molecule –> cannot leave ER and are bare leading to chronic viral infections

Question 25

What cause Bare Lymphocyte Syndrome Class II?

Answer 25

Inherited defect in CIITA (transactivator induced by IFNgamma) leading to deficiency in HLA class II and on function T lymphocytes (decreased humoral responses because reduced antigen presentation to mature CD4+)