7. ANTIGEN PRESENTATION

148

Antigen presentation

Fig. 7.3 Mononuclear phagocytes (1), B cells (2), and DCs (3)can all present antigen to MHC class II restricted TH cells.Macrophages take up bacteria or particulate antigen via non-specific receptors or as immune complexes, process it, andreturn fragments to the cell surface in association with MHCclass II molecules. Activated B cells can take up antigen viatheir surface immunoglobulin and present it to T cellsassociated with their MHC class II molecules. DCsconstitutively express MHC class II molecules and take upantigen by macropinocytosis.

mononuclear phagocytes

TH

phagolysosome

non-specificreceptor

MHCclass II

molecule

antigen

specific antigen uptake

surfaceimmunoglobulin

pinocytosis

B cells

dendritic cells

Fc receptor

antigen

TH

1

2

3

THB

Antigen-presenting cells

Fig. 7.4 Many APCs are unable to phagocytose antigen, butcan take it up in other ways, such as by pinocytosis.Endothelial cells (not normally considered to be APCs) thathave been induced to express MHC class II molecules byinterferon- (IFN) are also capable of acting as APCs, as aresome epithelial cells. Another example is the thyroid follicularcell, which acts as an APC in the pathogenesis of Gravesautoimmune thyroiditis.

phago-cytosis

type location class IIexpression

phagocytes(monocyte/macrophagelineage)

non-phagocyticconstitutiveAPCs

lymphocytes

facultativeAPCs

constitutive

monocytes

astrocytes

macrophages

marginal zonemacrophages

Kupffer cells

Langerhanscells

interdigitatingDCs (IDCs)

folliculardendritic cells

B cells andT cells

follicular cells

fibroblasts

other types inappropriate tissue

bloodtissue

spleen andlymph node

liver

skin

lymphoidtissue

lymphoidtissue

lymphoidtissues

and at sitesof immunereactions

brain

thyroid

vascular andlymphoid

tissueconnective

tissue

inducible

inducible

( )inducible

inducible

inducible

microglia

endothelium

brain

T cell antigenic peptides in the repressor protein Fig. 7.5 Diversity of antigenic peptides inrelation to MHC class II molecules. Micewere immunized with repressor protein.T cell hybridomas generated from mousecells were tested against a panel ofoverlapping peptides, which spanned theentire protein. Positions of antigenicpeptides are shown in dark blue. Onepeptide was always immunodominant,though more than one peptide wasantigenic in some mouse strains. Usuallyonly a few peptides from a protein arestimulators. (Adapted from data of Roy S,Scherer MT, Briner TJ, et al. Science1989;244:572575)

100%

strain

BALB/c

C57BL/6

B10.BR

B10

SM/J

% = % of hybridomas recognizing both the protein and the peptide

haplotype

d

b

k

s

v

20%

!92%

!96%

N

1 20 30 40 50 60 7010 80 90 102

50% 30%

50% 50%

antigenic peptide position

C