Antigen presenting cells and

antigen presentation

Antigen presenting cells

Antigen presentation

Contents

A variety of cell types which

carry antigen in a form that can

stimulate lymphocytes. It is also

termed accessory cell.

professional APC:MΦ,DC,B

non-professional APC

Antigen presenting cell, APC

The 3 types of professional APCs

Constitutively express a high level of MHC II and the co-stimulatory protein,B7. the most effective APC

Constitutively express class II MHC but must be activated to produce B7.

must be activated by the process of phagocytosis before expressing class II MHC and B7.

I. Dendritic cells (DC)

Dendritic cells were first described by Paul Langerhans (Langerhans cells) in the late nineteenth century. It wasn't until 1973, however, that the term "dendritic cells" was coined by Ralph M. Steinman and Zanvil A. Cohn. In 2007 Steinman was awarded the Albert Lasker Award for Basic Medical Research for his discovery.

MarksMouse 33D1,NLDC145Rat OX62Human CD1a,CD11c,CD83Other marks:MHCⅡ,CD80,CD86

Sources of DC

单 核细 胞

巨 噬细 胞

中 性粒 细 胞

B细 胞T细 胞NK细 胞

髓 系 DC

BTN K

髓 系 DC

淋 巴系 DC

淋 巴 系 前 体 细 胞

髓 系前 体 细胞

多 能造 血 干细 胞

GM-CSFTNF-IL-4

HSC

Myeloid progenitor

Lymphoid progenitor

DC Mo

macrophageDC

PMN

DC

                                                                                                                                                             

Dendritic Cell Maturation

LPS

IL-1,TNFα

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Functions of DC: antigen presentation, immune activation, immune tolerance

mononuclear phagocyte system, MPS

1.Differentiation and distribution

2. Surface markers

3. function

Antigen presenting cells

Bone marrow Blood tissues

HSC

Myeloid progenitor

Pre-monocyte

monocyte

monocyte macrophage

Differentiation and distribution of MPS

1. Surface markers:

MHC-I/ moleculesⅡ CKR: M-CSFR

CAM: LFA-1,ICAM-1,B7,CD40

FcR, CR1/3/4 2. secretion ： -enzymes: lysosome , myeloperoxidase

-cytokines (IL-1,TNF,IL-12)

-complement:C1 ～ C9, Bf

-coagulation factor, PG, LTs, ACTH, etc.

Mononuclear phagocyte system, MPS

Biological functions of MPS Phagocytosis antitumor ： indirect or direct killing, ADCC; participating in immune response： -Ag presenting, providing the second signal； -CMI participating in immune regulation:

-positive regulation ： secrete IL-1/12 ， TNF-α

-negative regulation ： PG, TGF-β Mediating inflammation: phagocytosis, secrete

inflammation medium

phagocytosis

Antigen presenting cells

B cells

The properties of various APCs

DefinitionAPCAg presentation -MHC class I molecule pathway -MHC class II molecule pathway

Ag presentation

Antigen capturingPhagocytosisPinocytosisReceptor-mediated endocytosis

Antigen processing

The conversion of an

antigen into a form in which it can

be recognized by lymphocytes.

Antigen presentation

The process by which certain cells in the

body (APC) express antigen peptide-MHC

molecule complex on their cell surface in a

form recognize by lymphocytes.

Recourses of antigens* exogenous antigen

* endogenous antigen

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

Y

Cytosolic compartmentEndogenous processing

(Viral antigens)

Vesicular CompartmentContiguous with extracellular fluid

Exogenous processing(Streptococcal, Mycobacterial antigens)

Distinct mechanisms of antigen generation are used to raiseT cells suited to the elimination of endogenous or exogenous pathogens

INTRACELLULAR REPLICATION

EXTRACELLULAR ORENDOSOMAL REPLICATION

Pathogens in Cytosol/Vesicles

The pathway of MHC I -associated endogenous Ag presentation

endogenous antigen （ such as virus Ag, tumor Ag)

cytoplasm degraded by proteasome

antigen peptide （ 8-13 AA ） 　 transported to endoplasmic

reticulum by TAP

Peptide/MHC-I molecule complex

to surface of APC

submit to CD8+T

Degradation in the proteasome

The components of the proteasome include MECL-1, LMP2, LMP7These components are induced by IFN- and replace constitutive

components to confer proteolytic properties.

LMP2 & 7 encoded in the MHC

Proteasome cleaves proteins after hydrophobic and basic amino acids and releases peptides into the cytoplasm

Cytoplasmic cellular proteins, including non-self proteinsare degraded continuously by a multicatalytic protease of 28 subunits

ER membrane

Lumen of ER

Cytosol

Transporters associated withantigen processing (TAP1 & 2)

Transporter has preference for >8 amino acid peptideswith hydrophobic C termini.

TAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

TAP-1 TAP-2

Peptide

ER membrane

Lumen of ER

Cytosol

TAP-1 TAP-2

Peptide

ATP-binding cassette(ABC) domain

Hydrophobictransmembranedomain

Peptide antigensfrom proteasome

Endoplasmic reticulum

Calnexin bindsto nascent

class I chainuntil 2-M binds

TAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

TAP-1 TAP-2

PeptideTAP-1 TAP-2

Peptide

B2-M binds and stabilises

floppy MHC

Tapasin, calreticulin, TAP 1 & 2 form a complex with

the floppy MHC

Cytoplasmic peptides are loaded onto the

MHC molecule and the structure becomes

compact

Maturation and loading of MHC class I

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The pathway of MHC II -associated exogenous Ag presentation

Exogenous antigen newly synthesised MHC class II molecule （ in the endoplasmic reticulum ）

early endosome li binds in the groove of MHC class II molecule

lysosome protease MIIC

late endosome li degrade

protease

Degrade into 1318AA peptide + MHC class II molecule Ag peptide/MHC class II molecule complex

transport to the surface of APC, recognized by CD4+T

Phagocytosis, pinocytosis,

FcR-phagocytosis

Y Y

Pinocytosis

Phagocytosis

Membrane Igreceptor mediateduptake

Y

Uptake of exogenous antigens

Complement receptormediated phagocytosis Y

Fc receptor mediated phagocytosis

opsonization

Proteases produce ~24 amino acid long peptides from antigensDrugs that raise the pH of endosomes inhibit antigen processing

Endosomes

Exogenous pathway

Increasein acidity

To lysosomes

UptakeProtein antigens

In endosome

Cathepsin B, D and L proteases are activated by the decrease in pH

involve in the assembling and folding of MHC class II molecule; Block the groove of MHC class II molecule; Lead the assembled class II molecule to M C.Ⅱ

The functions of Ii:

CLIP ： class II-associated invariant chain peptide

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Cross-presentation

Class I MHC molecules present exogenous Ags to CD8+ T cells

Cross-presentation of Ags by DC plays an important role in anti-viral infection and anti-tumor immunity.