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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Contents

1.Nature of antigen-presenting cells

2. Antigen processing and presentation

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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.

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Professional APC

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

Non-professional APC

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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.
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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)

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Tissue distribution :

Lymphoid DC:interdigitating DC, marginal DC

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

Humoral DC: veiled cell

Blood DC

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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.

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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

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Antigen uptaking pathways by DC
  • macropinocytosis
  • receptor-mediated endocytosis
  • phagocytosis
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2. Mononuclear macrophages

M:

Origination and distribution

Bone marrow pluripotent stem cells-mononuclear cells-macrophages

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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.

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Macrophagocytosis

mIg mediated endocytosis

Complement receptor mediated endocytosis

Pinocytosis

Fc receptor mediated endocytosis

Uptake of exogenous antigens

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3 B lymphocytes

Receptor-mediated endocytosis

Non-specific pinocytosis

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Dendritic cell

macrophage

B cell

Staining of APC

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DC capture antigens :

Macropinocytosis

Receptor-mediated endocytosis

Phagocytosis

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Mononuclear macrophage capture antigens:

Phagocytosis

Pinocytosis

Receptor-mediated endocytosis

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B cells captureantigens:

Non-specific pinocytosis

Antigen-specific receptor mediated

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2. Antigen processing

1、Endogenous pathway

Antigens: intracellular synthesized antigens

Presenting molecules:MHC-I

Processing region: Proteosome (polyubiquitination)

Binding region: ER

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Cell surface

cytoplasm

Golgi complex

Endoplasmic reticulum

calnexin

MHC Ia chain

Degraded antigens

proteasome

Endogenous antigens

Processing and presentation of endogenous antigens

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(1) Production of endogenous antigenic peptide

Ubiquitination of endogenous antigens

Degradation of endogenous antigens in proteosome

Peptides containing 8-12 amino acidresidues

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(2) Transportation of endogenous antigenic peptide

Endogenous antigenic peptide enter endoplasmic reticulum:

Transporter associated with antigen processing(TAP)

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(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

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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

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2. Presenting pathway of exogenous antigens(Exogenous pathway)

Antigen: extracellular antigens

Presenting molecules: MHC-II

Processing region: endosome

Binding region: MIIC、CIIV

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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

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Antigen processing compartment

Endosome

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

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(2)Degradation of protein antigen

Peptides containing 12-20 amino acid residues

Endopeptidase

Exopeptidase

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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

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Function of Ii

To prevent degradation of MHC class II molecule during its transportation

CLIP binds to the grooves in MHC class II molecule

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(4)Ii degradation in endosome

(5)Class II molecules peptide loading

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(6)Presentation of exogenous antigens

Exocytic vesicles

Expressed on APC

Recognized by CD4+ T cells

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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

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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

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3. Antigen presentation

1. Basic procedure of antigen presentation

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CD8+ T cells

Tumor cells

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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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