Antigen Capture and Presentation to Lymphocytes

Question 1

describe how B and T lymphocytes differ in the type of antigen they recognize

Answer 1

• B-cells:
  
  • protein, polysaccharides, lipids, nucleic acid
  • soluble form or cell surface-associated antigens
• T-cells
  
  • peptide fragments of protein antigens
  • only when presented on specialized molecules

Question 2

describe T-cell antigen presentation by dendritic cells

Answer 2

• dendritic cell in epithelium: capture microbial antigen
• activation of dendritic cells
• migration to draining lymph node (chemokines)
• maturation: due to cytokines and TLR-signaling
• expression of MHCII and co-stimulators for stimulation of T cells

Question 3

contrast the MHC I pathway vs the MHC II pathway

Answer 3

Question 4

describe class I MHC

Answer 4

MHC I are expressed on the majority of nucleated cells

• heterodimeric protein (Ig superfamily)
  
  • alpha chain
    
    • transmembrane
    • encoded by A, B and C regions in human MHC complex
  • beta chain: B2-microglobulin
    
    • encoded by highly conserved gene on different chromosome

Question 5

describe MHC I peptide binding

Answer 5

• α1/α2 highly polymorphic peptide-binding region
• α3 binds to CD8 on cytotoxic T cells
• bind short peptides, usually between 8-10 amino acids
• presents an endogenously processed antigens

Question 6

describe the class II MHC protein

Answer 6

MHC II expessed on antigen presenting cells (APC)

• heterodimeric protein (Ig superfamily)
  
  • α1 and α2 chain
    
    • transmembrane
  • β1 and β2 chain
    
    • transmembrane

Question 7

describe MHC II peptide binding

Answer 7

• α1/β1, highlypolymorphic peptide-binding region
• β2, highly conserved, binds to CD4 on helper T cells
• α2, highly conserved
• bind long peptides, usually between 13-25 amino acids
• present Ag of extracellular origin

Question 8

describe MHC restriction

Answer 8

• CD8+ Tc cells are MHC class I restricted
  
  • can only recognize antigen presented by MHC class I molecules
  • therefore, cells with MHC class I are called “target cells” killed by cytotoxic T cells
• CD4+ Th cells are MHC class II restricted
  
  • cells with MHC class II are called antigen-presenting cells (APCs)

Question 9

explain the mechanism of action of CD4+ T cells and CD8+ T cells

Answer 9

Question 10

describe how the site of pathogen replication or mechanism of antigen uptake determines the antigen processing pathway used

Answer 10

Question 11

describe how antigens generated by endogenous vs exogenous antigen processing activate different effector functions

Answer 11

Question 12

contrast the cytosolic pathway vs. the endocytic pathway

Answer 12

• cytosolic pathway (endogenous, non-lysosomal)
  
  • endogenous antigens–produced in cell, in infected cell
  • antigens presented to Tc cells by MHC class I
• endocytic pathway (exogenous, lysosomal)
  
  • exogenous antigen–taken in by endocytosis by antigen-presenting cells
  • antigens presented to Th cells by MHC class II

Question 13

describe the endogenous processing of Ag

Answer 13

• proteins targeted for lysis are tagged with ubiquitin
• the protein is then degraded by the proteasome
  
  • the components of the proteasome include MECL-1, LMP2, LMP7
  • these components are induced by IFN-gamma
• peptides need access to the ER in order to be loaded onto MHC class I molecules
  
  • transporters associated with antigen processing (TAP1 & 2)
• cytoplsamic peptides are loaded onto the MHC molecule and the structure becomes compact and exported to the cell surface

Question 14

describe the evasion of immunity by interference with endogenous antigen processing

Answer 14

• many viruses produce immunoevasins that interfere with antigen presentation by MHC class I molecules
  
  • viruses block MHC class I from properly presenting them to CD8 T cells
    
    • inhibit peptide transport
    • inhibit peptide loading
    • cause MHC class I degradation

Question 15

describe the cytosolic pathway

Answer 15

Question 16

describe non-lysosomal antigen processing from inactive vs active viruses

Answer 16

• inactive viruses raise a weak CTL response
• the processing of antigens from inactive viruses is sensitive to lysosomotrophic drugs (increase pH on endosome)
• antigens from inactive viruses are processed via the exogenous pathway (MHC class II presentation)
• infectious virus raises a strong CTL resposne
• the processing of antigens from infectious viruses is NOT sensitive to lysosomotrophic drugs
• protein synthesis is required for non-lysosomal antigen processing
• antigens from infectious viruses are processed via the endogenous pathway (MHC class I presentation)

Question 17

summarize the endocytic/exogenous pathway

Answer 17

Question 18

describe bacteria evasion of MHC II antigen presentation

Answer 18

• escape endosomes
• neutralize endosome acidification
• block fusion with lysosome
• sequesters MHC class II molecules after vesicle fusion, preventing from going to the surface

Question 19

describe cross-presentation, cross-priming and an example

Answer 19

• cross presentation
  
  • exogenous antigens normally processed by phagolysosomes (MHC-II) are presented by MHC-I (exception to the MHC class I rule)
• cross-priming
  
  • then presented to and activate CD8+ T-cell
• example:
  
  • Rickettsia rickettsia
  • endocytosed but rapidly lyse endosomal membrane and escape prior to phagolysosome formation
  • degraded by proteasome and presented on MHC I