Antigen presenting cells and antigen presentation
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Antigen-presenting cells and antigen presentation. Contents. 1.Nature of antigen-presenting cells 2. Antigen processing and presentation. Antigen Presenting Cell (APC). Section 1 Nature of antigen-presenting cells.

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Antigen presenting cells and antigen presentation

Antigen-presenting cells and antigen presentation


Antigen presenting cells and antigen presentation

Contents

1.Nature of antigen-presenting cells

2. Antigen processing and presentation


Antigen presenting cells and antigen presentation

Antigen Presenting Cell (APC)


Antigen presenting cells and antigen presentation

Section 1 Nature of antigen-presenting cells

Antigen-presenting cells (Antigen Presenting Cell, APC) are the immunocytes that can uptake, process and present antigens to lymphocytes.


Antigen presenting cells and antigen presentation

Professional APC

Dendritic cells, mononuclear phagocyte system, B cells, and APC that constitutively express MHC II molecules

Non-professional APC


Antigen presenting cells and antigen presentation

Dendritic cells


Antigen presenting cells and antigen presentation

DC are the most powerful APC in vivo, which can effectively stimulate naïve T cells to proliferate. Yet M and B cells can only stimulate activated or memory T cells.


Antigen presenting cells and antigen presentation

Multiple hematopoietic stem cell

Lymphoid stem cell

Myeloid stem cell

Neutrophil

Myeloid DC

Monocyte

NK cell

Lymphoid DC

T cell

B cell

Macrophage

Myeloid DC

Origination of dendritic cells(DC)


Antigen presenting cells and antigen presentation

Tissue distribution :

Lymphoid DC:interdigitating DC, marginal DC

Non-lymphoid DC: interstitial DC, LC, gastrointestinal epithelial DC

Humoral DC: veiled cell

Blood DC


Antigen presenting cells and antigen presentation

  • Differentiation and development of DC

  • precusor

  • immature stage (immature DC)

  • migratory stage

  • mature stage(mature DC)

Immature DC

Distribution: many solid organs and non lymphatic epithelia

Major role: uptake and process antigen

Normally, most DC are immature DC.


Antigen presenting cells and antigen presentation

Mature DC

Distribution: T lymphocyte areas in lymph node, spleen, and Peyer’s node, blood

Characteristics: abundantly express MHC II、MHC I、CD80、CD86、CD40、ICAM-1、HSP、CD1a、CD11c、CD83

Major role: antigen presentation, present peptide:MHC complex to T cells


Antigen presenting cells and antigen presentation

Antigen uptaking pathways by DC

  • macropinocytosis

  • receptor-mediated endocytosis

  • phagocytosis


Antigen presenting cells and antigen presentation

2. Mononuclear macrophages

M:

Origination and distribution

Bone marrow pluripotent stem cells-mononuclear cells-macrophages


Antigen presenting cells and antigen presentation

Antigen processing and presentation of M

  • endocytosis or internalization:

  • phagocytosis

  • Pinocytosis

  • receptor-mediated endocytosis

    Only those M in vigorous metabolism have the capacity of antigen presentation.


Antigen presenting cells and antigen presentation

Macrophagocytosis

mIg mediated endocytosis

Complement receptor mediated endocytosis

Pinocytosis

Fc receptor mediated endocytosis

Uptake of exogenous antigens


Antigen presenting cells and antigen presentation

3 B lymphocytes

Receptor-mediated endocytosis

Non-specific pinocytosis


Antigen presenting cells and antigen presentation

Dendritic cell

macrophage

B cell

Staining of APC


Antigen presenting cells and antigen presentation

Section 2 Antigen processing and presentation

1 Antigen uptaking


Antigen presenting cells and antigen presentation

DC capture antigens :

Macropinocytosis

Receptor-mediated endocytosis

Phagocytosis


Antigen presenting cells and antigen presentation

Mononuclear macrophage capture antigens:

Phagocytosis

Pinocytosis

Receptor-mediated endocytosis


Antigen presenting cells and antigen presentation

B cells captureantigens:

Non-specific pinocytosis

Antigen-specific receptor mediated


Antigen presenting cells and antigen presentation

2. Antigen processing

1、Endogenous pathway

Antigens: intracellular synthesized antigens

Presenting molecules:MHC-I

Processing region: Proteosome (polyubiquitination)

Binding region: ER


Antigen presenting cells and antigen presentation

Cell surface

cytoplasm

Golgi complex

Endoplasmic reticulum

calnexin

MHC Ia chain

Degraded antigens

proteasome

Endogenous antigens

Processing and presentation of endogenous antigens


Antigen presenting cells and antigen presentation

(1) Production of endogenous antigenic peptide

Ubiquitination of endogenous antigens

Degradation of endogenous antigens in proteosome

Peptides containing 8-12 amino acidresidues


Antigen presenting cells and antigen presentation

(2) Transportation of endogenous antigenic peptide

Endogenous antigenic peptide enter endoplasmic reticulum:

Transporter associated with antigen processing(TAP)


Antigen presenting cells and antigen presentation

Schematic diagram of TAP structure


Antigen presenting cells and antigen presentation

(3) MHC class I molecules peptide loading

Class I molecules associate with chaperon:

Bind to endogenous antigenic peptides

Enter Golgi complex to undergo glycosylation modification

Traffick to cell surface in exocytic vesicles and recognized by CD8+ T cells


Antigen presenting cells and antigen presentation

Membrane

Antigen-MHC class 1 molecule complex

β2 microglobulin

Heavy chain of antigen-MHC class 1 molecule

Golgi complex

β2 microglobulin

Calnexin

Antigenic peptide

Endogenous antigen

Presentation of endogenous antigens

Proteasome


Antigen presenting cells and antigen presentation

2. Presenting pathway of exogenous antigens(Exogenous pathway)

Antigen: extracellular antigens

Presenting molecules: MHC-II

Processing region: endosome

Binding region: MIIC、CIIV


Antigen presenting cells and antigen presentation

Cell surface

Exogenous antigens

Fusion

Early endosome

Late endosome

Antigen degradation

Golgi complex

MHC class 2 molecule

Ii chain

Endoplasmic reticulum

Processing and presentation of exogenous antigens


Antigen presenting cells and antigen presentation

Antigen processing compartment

Endosome

MHC class II、HLA-DM, and exogenous antigenic peptide are found in abundance.


Antigen presenting cells and antigen presentation

(2)Degradation of protein antigen

Peptides containing 12-20 amino acid residues

Endopeptidase

Exopeptidase


Antigen presenting cells and antigen presentation

MHC class II molecules are transported from ER to endosome.

Calnexin

Ia associated invariant chain(Ii chain):

Class II associated invariant chain peptide (CLIP)

Form nonamer with ,  chain

Enter endosome through trans-Golgi network


Antigen presenting cells and antigen presentation

Function of Ii

To prevent degradation of MHC class II molecule during its transportation

CLIP binds to the grooves in MHC class II molecule


Antigen presenting cells and antigen presentation

(4)Ii degradation in endosome

(5)Class II molecules peptide loading


Antigen presenting cells and antigen presentation

Class II molecules peptide loading


Antigen presenting cells and antigen presentation

(6)Presentation of exogenous antigens

Exocytic vesicles

Expressed on APC

Recognized by CD4+ T cells


Antigen presenting cells and antigen presentation

Antigen

Antigen

Antigenic peptide-MHC class 2 molecule complex

internalization

Phagocytosis

B cell

Macrophage

Endosome/lysosome

Golgi complex

ER

Antigenic peptide-MHC class 2 molecule complex

αβIi complex

Ii chain

Presentation of exogenous antigens


Antigen presenting cells and antigen presentation

Comparison of endogenous and exogenous antigen-presenting pathway

Characteristics Endogenous pathway exogenous pathway

Presenting molecule MHC-I MHC-II

Responding T cells CD8+ T cells CD4+ T cells

Antigen resources endogenously synthesized exogenous uptaken

Synthesizing region

of antigen peptides proteosome endosome

Chaperon Calnexin, TAP, tapasin Calnexin, Ii chain

Presenting cells all nucleated cells professional APC


Antigen presenting cells and antigen presentation

3. Antigen presentation

1. Basic procedure of antigen presentation


Antigen presenting cells and antigen presentation

CD8+ T cells

Tumor cells


Antigen presenting cells and antigen presentation

2.Cross presentation of antigens by MHC molecules

(Cross priming pathway)


Antigen presenting cells and antigen presentation

  • Master cell types, definition and characteristics of APC

  • Master types of professional APC

  • Master the pathway and procedure of exogenous and endogenous antigen presentation

  • Familiarize antigen cross presentation

  • Understand the distribution and characteristics of various kinds of professional APC

  • Understand development, differentiation, maturation and migration of DC


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