Antigen presenting cells and antigen presentation

T cells do not recognise native antigens Y Y B Y Y Y Y Y Y Y B Y 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 Concepts Endogenous antigens: antigens produced within cells Exogenous antigens: antigens internalized by endocytosis Ag capturing Endocytosis Phagocytosis Pinocytosis Receptor-mediated endocytosis Ag processing and Ag presentation APC

I. Antigen presenting cells Concepts Endogenous antigens: antigens produced within cells Exogenous antigens: antigens internalized by endocytosis Ag capturing Endocytosis Phagocytosis Pinocytosis Receptor-mediated endocytosis Ag processing and Ag presentation A protein antigen be degraded into peptides by a sequence of events The degraded peptides associate with MHC molecules, and 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 antigens Site of infection peripheral lymphoid organ Peripheral tissue

Antigen-presenting cells cells 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-presenting 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 molecules 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 DC Lymphoid DC By mature Immature DC Mature DC

1. Dendritic cells Dendritic cells are bone marrow-derived cells Classification By source Myeloid DC Lymphoid DC By mature Immature DC Mature DC By distribution Lymphoid tissues Interdigitating 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 antigens 2. Presenting antigens During 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 of particulate antigens before they express class II MHC molecules 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 granules pinocytosis: liquids receptor-mediated endocytosis: specific exogenous antigen Endosome A vesicle is formed by partial cell membrane which surrounds the endocytosed antigens

Endosome A 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 complex The 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 proteosome A multifunctional protease complex immunoproteosome A proteosome containing three subunits, PMSB- 8,PMSB-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 molecules calnexin --- α chain of MHC molecule calreticulin tapasin 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