Antigen processing/recognition by T lymphocytes Flashcards
B cells can bind to _____, while T cells need to be_____
Native antigens; introduced to antigens thru APCs
TCR antigen recognition
Only in the form of peptide bound to an MHC molecule on the surface of APC
Antigen processing
Pathogen-derived proteins must be degraded into peptides
Peptide:MHC complex
Displayed on APC surfaces, where they can be recognized by T cells
Antigen presentation
Binding of peptide:MHC complex and its expression on APC
2 classes of MHC
MHC molecules bind a variety of peptides in different intracellular compartments
- CD8 binds alpha-3 domain of MHC class 1
- CD4 binds the beta-2 domain of MHC class 2
TCR specifically binds ______
BOTH peptide and MHC molecules
Professional antigen-presenting cells
- dendritic cells
- macrphage
- B cell
Dendritic cell
- Cell type: viral
- Location in lymph node: T cell area
- Antigen uptake: macropinocytosis/phagocytosis (+++) universal antigen uptake
- MHC expression: low on tissue DCs, high on lymphoid tissue DCs
- Co stimulator delivery: constitutive, nonphagocytic lymphoid DCs (++++)
- Antigen presented: peptides, viral, allergens
- Location: ubiquitous
Macrophage
- Cell type: bacterium
- Location in lymph node: ??
- Antigen uptake: phagocytosis (+++)
- MHC expression: inducible by bacteria and cytokines (- to +++)
- Co stimulator delivery: Inducible (- to +++)
- Antigen presented: particulate antigens, intra/extracellular pathogens
- Location: lymphoid tissue, connective tissue, body cavity
B cell
- Cell type: microbial toxin
- Location in lymph node: follicle
- Antigen uptake: antigen-specific receptor (++++)
- MHC expression: constitutive, increases on activation (+++ to ++++)
- Co stimulator delivery: inducible (- to +++)
- Antigen presented: soluble antigens, toxins, viruses
- Location: lymphoid tissue, peripheral blood
What cell type is the best APC?
Dendritic cells
- are widely distributed in the body, can present any possible antigen derived peptide
What makes a cell “professional”?
Able to activate T cells
What is the difference between immature and mature cells?
Immature: uptake and process antigens (little MHC class 2)
Mature: present antigen (lots of MHC class 2)
How do DC mature?
DC take up bacterial antigens in the skin and then move to enter a draining lymphatic vessel –> DCs bearing antigen enter draining lymph node where they settle in the T cell areas
mature on taking antigen from infected sites to secondary lymphoid organs
Where is MHC located in immature T cells?
All MHC class 2 are inside, as MHC moves to the surface the cell matures
Classical model
Migration of immature DC from the periphery to the T cell areas of the lymph nodes only occurs in response to microbial stimulation
- pathogen induced migration
Revised model
Steady state migration occurs constitutively in the apparent absence of microbial stimulation
- mechanism by which DC can sample and engulf self proteins and food antigens to naive T cells to establish/maintain peripheral tolerance
- pathogen induced migration
Direct presentation
Peptides generated in cytosol are transported to ER, where they bind MHC class 1 molecules and presented to CD8+ T cells
Direct presentation (CD4)
Peptides generated in acidified intracellular vesicles presented by MHC class 2 molecules to CD4+ T cells
Cross presentation
Allows extracellular antigens to be processed and displayed within MHC class 1 molecules to CD8+ T cells (in addition to MHC class 2 and CD4+ T cells)
Receptor mediated endocytosis of bacteria
- MHC class 2
- CD4 T cell
Marcopinocytosis of bacteria or viruses
- MHC class 2
- CD4 T cell
Viral infection
- MHC class 1
- CD8 T cell
Cross presentation of exogenous viral antigens
- MHC class 1
- CD8 T cell
Transfer of viral antigens from infected DC to resident DC
- MHC class 1
- CD8 T cell
Questions that only cross presentation can answer
- How to CD8+ T cell responses are primed to infectious organisms that do not infect APCs?
- How can DCs prime cytotoxic T cells against pathogens that are restricted to the endocytic pathway and never reach the cytosol?
- Pathogen infected DCs are often functionally compromised, how can they present antigens efficiently?
Autophagy
Presentation of cellular antigens by MHC class 2 molecules
Exceptions to the rules of antigen presentation
- cross presentation
- autophagy
Why is yeast used in immunology research?
Can generate multiple clones quickly
How does autophagy control innate and adaptive immunity?
- direct pathogen elimination
- regulation and effector function of PRRs
- regulation of inflammasome activation and alarmin secretion
- cytoplasmic Ag processing for MHC 2 presentation and T cell homeostasis
Macroautophagy
immunological autophagy
How are MHC 1 molecules expressed on APCs
+++ on T cells, B cells, macrophages, DC, and neutrophils
+ on thymic epithelium, liver hepatocytes, kidney epithelium, and brain
How are MHC 2 molecules expressed on APCs
+++ on B cells and DC
+ on T cells
++ on macrophages
+++ on thymic epithelium
Erythrocytes
Do not express either MHC 1 or 2
Degenerate (promiscuous) binding specificity
MHC molecules have peptide binding sites that are capable of binding peptides of many different amino acid sequences
- MHC have germline configuration = less diversity, so they need to be promiscuous
Peptide binding groove
Peptide binding site on the surface of the MHC molecule within which a single peptide is held tightly by non covalent bonds
What do alpha/beta TCRs recognize?
Peptide presented at cell surfaces by MHC molecules
Where do peptides bind to MHC class 1?
Endoplasmic reticulum
Where are MHC class 2 peptides generated?
In acidified intracellular vesicles
Cross presentation enables ____
Professional APCs to stimulate cytotoxic CD8 T cell responses against viruses that do not infect them directly
