12. antigen processing & presentation to T lymphocytes

where does antigen presentation occur during the initiation of T cell responses?

secondary lymphoid tissues (spleen, lymph nodes) to naive T cells

where does antigen presentation to effector T cells occur?

can occur in all tissues

antigen presentation by migratory dendritic cells

• antigens are captured by dendritic cells → become activated

• dendritic cells migrate to paracortex (lymph nodes)

• present antigen to naive T cell

vesicular cellular compartment

• membrane-bound organelles (separated by membranes)

• communicates with extracellular environment → endo/exocytosis

• ex. golgi, endosomes, lysosomes

cytosolic cellular compartment

communicates intracellularly → between nucleus & cytoplasm

what two important factors regulate the pathway of antigen processing & presentation?

1. source of proteins

   • extracellular

   • intracellular

2. intracellular location of the protein

   • endosomes

   • cytoplasm

extracellular/vesicular antigens are processed by what pathway?

exogenous/endocytic pathway - MHC II (presented to CD4+ cells)

what type of vaccines utilize the exogenous/endocytic pathway?

inactivated or purified protein vaccines

cytosolic antigens are processed by what pathway?

endogenous/cytosolic pathway - MHC I (presented CD8+ cells)

what types of vaccines utilize the endogenous/cytosolic pathway?

• live viral/vectored vaccines

• mRNA vaccines

what is cross presentation?

extracellular protein processed through the endogenous/cytosolic pathway → MHC I → present to CD8+ cells

what cells can cross-present?

dendritic cells only

which cells can present antigen to CD8+ T cells?

all nucleated cells (express MHC I)

ubiquitin

when conjugated to other proteins, flags protein for degradation

proteasome

filled with proteases → cytosolic proteolysis 

MHC I (endogenous/cytosolic) pathway general steps

1. proteolytic degradation of proteins

2. peptides transported from cytosol to rough ER

3. complexes with MHC I in the ER

4. peptide-MHC complex packaged into exocytic vesicles and expressed on surface

what do chaperone proteins do?

stimulate α and β chains of MHC molecules to complex together in ER

transporters associated with antigen processing (TAP) - TAP1 & TAP2

translocate peptides from cytoplasm into ER for loading on to MHC class I molecules

what is the physiological significance of MHC I-associated antigen presentation?

cell killing by CD8+ cytotoxic T lymphocytes

what cells can present antigens to CD4+ T cells?

professional antigen presenting cells

• dendritic cells

• macrophages

• B cells

why can professional antigen presenting cells present to CD4+ cells?

1. express MHC II molecules

2. ability to perform endocytosis

3. ability to process endocytosed antigens

MHC II (exogenous/endocytic) pathway general steps

1. proteins broken down by proteases in endosome

2. MHCII transported from ER to endosome

3. proteolytic degradation of invariant chain & CLIP removal

4. peptide-MHC interaction

5. expression on cell surface

invariant chain

• prevents peptide loading onto class II molecules in ER (blocks peptide binding groove)

• involved in trafficking of MHC molecules to peptide-containing acidified endosomes

class II-associated invariant chain peptide (CLIP)

piece of invariant chain that remains in peptide binding groove after proteolytic degradation

HLA-DM

catalyzes removal of CLIP from peptide binding groove to allow peptide loading onto MHC II molecule

what is the physiological significance of MHC II-associated antigen presentation?

• immune response against extracellular pathogens

• production of antibodies

  • B cells present peptide-MHC complex to T cells → T cells help B cells produce Abs

what is the physiologic significance of cross presentation?

present microbial/tumor antigens → prime CD8+ to target infected/neoplastic cells