Antigen Processing and Presentation Chapter 8 Antigen Recognition - - PowerPoint PPT Presentation

▶
antigen processing and presentation
SMART_READER_LITE
LIVE PREVIEW

Antigen Processing and Presentation Chapter 8 Antigen Recognition - - PowerPoint PPT Presentation

Oct 30, 2022 112 likes •555 views

Antigen Processing and Presentation Chapter 8 Antigen Recognition by T Cells T cells recognize linear peptides not whole proteins. T cells only recognize epitopes when they are complexed to MHC molecules. Therefore protein

slide-1
SLIDE 1

Antigen Processing and Presentation

Chapter 8

slide-2
SLIDE 2

Antigen Recognition by T Cells

  • T cells recognize linear peptides not whole proteins.
  • T cells only recognize epitopes when they are complexed to

MHC molecules.

  • Therefore protein antigens must be processed and

presented by other cells to be recognized by T cells.

  • This process is referred to as antigen processing and

presentation.

– Note: the association of antigenic peptides w/ MHC is a saturable, low-affinity interaction (Kd ~10-6M) with a slow

  • ff/on rate.
  • In general CD8+ T cells recognize endogenous antigens and

CD4+ T cells recognize exogenous antigens.

  • MHC molecules bind multiple peptides, however each T cell
  • nly recognizes one peptide.
slide-3
SLIDE 3

Assays for T cell Activation

Antigen APC Th cells Tc cells

Macrophage Dendritic Cell B cell

APC + Th + Ag

Proliferation (3H-thymidine uptake)

Tc + Target cell +Ag

Target cell lysis (51Cr release)

“Primed T cells”

slide-4
SLIDE 4
slide-5
SLIDE 5

T cells Macrophage

slide-6
SLIDE 6
slide-7
SLIDE 7
slide-8
SLIDE 8
slide-9
SLIDE 9
slide-10
SLIDE 10
slide-11
SLIDE 11

Figure 10-18

slide-12
SLIDE 12
slide-13
SLIDE 13
slide-14
SLIDE 14
slide-15
SLIDE 15
slide-16
SLIDE 16
slide-17
SLIDE 17
slide-18
SLIDE 18

Kloetzel, P.M., Nat. Immunol., 2004

slide-19
SLIDE 19

Proteosome Produces Epitopes Poorly

Ackerman and Cresswell, Nat. Immunol., 2004

slide-20
SLIDE 20

Proteosome Produces Epitopes Poorly

Ackerman and Cresswell, Nat. Immunol., 2004

slide-21
SLIDE 21

Epitope Destruction vs. Production

slide-22
SLIDE 22
slide-23
SLIDE 23

Epitope Destruction vs. Production

slide-24
SLIDE 24

Proteosome Produces Epitopes Poorly

Ackerman and Cresswell, Nat. Immunol., 2004

slide-25
SLIDE 25
slide-26
SLIDE 26
slide-27
SLIDE 27

Ackerman and Cresswell, Nat. Immunol., 2004

Peptide Loading Complex (PLC)

slide-28
SLIDE 28
slide-29
SLIDE 29
slide-30
SLIDE 30
slide-31
SLIDE 31

HLA-DM/H-2M

  • Acts as a catalyst to enhance the release
  • f CLIP
  • Does not bind antigenic peptides so does

not act as a peptide transfer molecule

  • Most efficient at low pH
  • Acts as a peptide editor, facilitating the

exchange of low stability, high off rate peptides for high stability peptides with a low off rate

slide-32
SLIDE 32

Role of DM in Peptide Loading

Brocke et al., 2002

slide-33
SLIDE 33

Interaction of DM and DO

Denzin et al., Science, 1997

[DM] DM + DO

Stability in SDS correlates with affinity for the bound peptide; binding to CLIP is of low affinity HLA-DR3αβ-CLIP + peptide + HLA-DM +/- HLA-DO

slide-34
SLIDE 34

t1/2= 26h t1/2= 86h t1/2= 1h t1/2= 65h

MHC Class II Peptide Stability Affect T cell Stimulation

slide-35
SLIDE 35

Cross-Presentation

  • Refers to the presentation of

exogenous antigens on MHC class I molecules.

slide-36
SLIDE 36
slide-37
SLIDE 37

Cross-Presentation

  • Refers to the presentation of

exogenous antigens on MHC class I molecules.

  • Exact mechanism is unclear; two

models have been proposed: recycling and ER loading.

slide-38
SLIDE 38

Cross Presentation Models

Jensen, 2007

slide-39
SLIDE 39

Cross-presentation: ER Model

Direct access to the ER via transiently available continuities

Ackerman and Cresswell, Nat. Immunol., 2004

slide-40
SLIDE 40

Cross-presentation: Phagosome Model

Sec61 associated phagosome

Ackerman and Cresswell, Nat. Immunol., 2004

slide-41
SLIDE 41
slide-42
SLIDE 42
slide-43
SLIDE 43