Antigen presenting cells and antigen presentation

T cells do not recognise native antigens

YY

BYY Y Y YY

Y

BY

T

Y

T

活化增殖、产生抗体

无增殖无 CK产生

BCR交联

Y

B

Y

B Y

B

Y

B

Y

B Y

B

Y

B

Processing and presentation of antigens

I. APC (antigen presenting cells)

II. Processing and presenting pathway

I. Antigen presenting cells ConceptsEndogenous antigens: antigens produced within cel

ls

Exogenous antigens: antigens internalized by endocytosis

Ag capturing-------Endocytosis Phagocytosis Pinocytosis Receptor-mediated endocytosisAg processing and Ag presentation

APC

I. Antigen presenting cells ConceptsEndogenous antigens: antigens produced within cellsExogenous antigens: antigens internalized by endocytosis Ag capturing-------Endocytosis Phagocytosis Pinocytosis Receptor-mediated endocytosis

Ag processing and Ag presentationA protein antigen be degraded into peptides by a sequen

ce of eventsThe degraded peptides associate with MHC molecules, a

nd the peptides-MHC molecule complexes are transported to the membrane, where they are displayed.

The process of immune response

Exogenous antigens Site of infection peripheral lymphoid organ

Peripheral tissue

Endogenous antigensSite of infection peripheral lymphoid organ

Peripheral tissue

Antigen-presenting cellscells that can process and present antigens (MHC-peptide) to T cells

Professional APC Dendritic cell Macrophage B lymphocyte

nonprofessional APC Several other cell types, classified as nonprofessional antigen-pre

senting cells, can be induced to express class II MHC molecules or a co-stimulatory signal Many of these cells function in antigen presentation only for short periods of time during a sustained inflammatory response.

APC APC can express MHC-II and co-stimulatory molecule

s and present exogenous antigens to CD4+ T cells, besides presenting endogenous antigens to CD8+ T cells.Three cell types are classified as professional antigen-presenting cells: dendritic cells, macrophages, and B lymphocytes.

1. Dendritic cells

Dendritic cells are bone marrow-derived cells

Classification By source Myeloid DCLymphoid DC

By matureImmature DCMature DC

1. Dendritic cellsDendritic cells are bone marrow-derived cells

Classification By source Myeloid DCLymphoid DC

By matureImmature DCMature DC

By distribution Lymphoid tissuesInterdigitating DC, follicular DC Non-lymphoid tissues Langerhans cell Body fluid

B cells

FDC

滤泡树突细胞（ follicular DC, FDC ）

淋巴滤泡内的 FDC 通过 Fc 受体和补体受体捕获被致敏的抗原，并将其递呈给 B细胞

并指状树突细胞（ interdigitating DC ）

IDC 表达高水平的 II类 MHC 分子和共刺激分子 B7，具有激活 T细胞的能力。

郎格汉斯细胞 (Langerhan’s cells)

上皮组织中的 LC, 捕捉外来抗原后即进入引流淋巴结的 T细胞区，成为 IDC

Function of DC :1. Capturing and processing antigens2. Presenting antigensDuring the maturation of DC , its ability of

Ag capture and processing decreased while its ability of Ag presenting give a rise.

Macrophages

Function : 1. Phagocytosis

2. Presentation of antigens Nonactivated macrophage

activated macrophage:

MHC II molecules

and costimulatory molecules

B cells

Functions Mediate humoral immune response

Present antigens to T cell

Soluble Ag

Specific receptor-mediated endocytosis

These cells differ from each other in their mechanisms of antigen uptake, in whether they constitutively express class II MHC molecules, and in their co-stimulatory activity:

•Dendritic cells are the most effective of the antigen presenting cells,constitutively expressing class II MHC molecules and the costimulatory B7 molecule.

•Macrophages must be activated by phagocytosis ofparticulate antigens before they express class II MHCmolecules or the co-stimulatory B7 membrane molecule.

•B cells constitutively express class II MHC molecules but must be activated before they express the co-stimulatory B7 molecule.

II. Processing and presentation pathway

MHC class II pathway-------exogenous antigens

MHC class I pathway-------endogenous antigens

Cross-presentation pathway

Non-classical pathway

MHC calss II pathway

1. Capture and processing of exogenous Ag

2. Synthesis and transportation of MHC II molecules

3. Formation of peptide - MHC II molecule complex

4.Presentation of peptide - MHC II molecule complex to CD4+ T cells

1. Capture and processing of exogenous Ag

Exogenous antigens are endocytosed and the endosome is formed

endocytosis:phagocytosis: particles or granulespinocytosis: liquids receptor-mediated endocytosis: specific exogenous antigen

EndosomeA vesicle is formed by partial cell membrane which surrounds the e

ndocytosed antigens

EndosomeA vesicle is formed by partial cell membrane which surrounds the endocytosed antigens

A phagolysome is formed when the endosome is fused with lysosome

cathepsins Ag antigen peptides

The antigen is hydrolysed into peptides by various proteases, such as cathepsins.

2. Synthesis and transportation of MHC II molecules

Synthesis of MHC II molecules in ER

Ii chain interacts with the pepetide-binding cleft of MHC II molecule ,Preventing any peptides from combining with MHC II molecules within ER

Ii leads MHC II molecules into endosome from ER via Golgi complex

Endosome (MIIC)

3. Formation of peptide - MHC II molecule complexThe Ii in the Ii-MHC II molecules complex is degraded in endosome

protease Ii chain cleaving

CLIP remains bound to the MHC class II molecules ( CLIP-MHC II molecules) HLA-DM catalyzes the exchange of CLIP with antigenic peptides.

HLA-DM CLIP releasing

Antigen peptide-MHC II molecules

4.Presentation of peptide - MHC II molecule complex to CD4+ T cells

antigen peptide-MHC II molecuels presented on cell membrane by exocytosis

MHC I pathway

1. Processing of endogenous Ag

2.transporting of antigen peptides into ER

3.Synthesis and assembly of MHC class I molecules

4. Formation and presentation of peptide- MHC molecules

1.Processing of endogenous Ag

proteosomeA multifunctional protease complex

immunoproteosomeA proteosome containing three subunits, PMSB-8,PMS

B-9 and PMSB-10 preferentially generate peptides that bind to MHC class I molecules.

Peptides that bind to MHCclass I molecules terminate almost exclusively with hydrophobic or basic residues.

2.transporting of antigen peptide into ER

TAP(transporter associated with antigen precessing): Consisting of TAP1 and TAP2 ATP dependent transporter Selective transporting

3. Synthesis and assembly of MHC class I molecules

chaperone moleculescalnexin--- α chain of MHC molecule

calreticulintapasin---------------α and β2 microglobulin

4. Formation and presentation of peptide- MHC molecules

As a consequence of peptide binding, the class I molecule displays increased stability and can dissoaciate from calreticulin and tapasin, exit from the ER and proceed to the cell surface via the Golgi.

ER Golgi complex Exocytic vesicles Cell membrane

Ag(cytosolic protein)

Proteasome proteolytic degradation

Ag peptide

TAP complex transporting into ER

antigen peptide-MHC I molecule

Golgi complex exocytosis

Presenting to CD8+ T cells

Cross-presentation pathwy

In contrast to traditional presentation, exogenous antigens are presented by MHC class I pathway, or endogenous antigens are presented by MHC class II pathway.

Processing and presentation of antigens

I. APC (antigen presenting cells)

II. Processing and presenting pathway