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ページの作成:「{{Floating_Menu}} ==MHC = HLA== *Major Histocompatibility Complex (MHC) is rephrased as Human Leukocyte Antigen (HLA) *Genetic loci are on 6th chromosome ==MHC and T ce…」
{{Floating_Menu}}
==MHC = HLA==
*Major Histocompatibility Complex (MHC) is rephrased as Human Leukocyte Antigen (HLA)
*Genetic loci are on 6th chromosome
==MHC and T cell receptor (TCR)==
*MHC presents peptide antigen and TCR recognize it
*'''CD8''' acts as co-receptor to '''MHC Class I''' on all '''target''' cells
*'''CD4''' acts as co-receptor to '''MHC Class II''' on '''antigen-presenting''' cells
{{#mermaid:
flowchart LR
subgraph ap[Antigen presenting cells]
direction LR
m2l["MHC Class II<br>α<sub>2</sub>β<sub>2</sub>"] --- m2u["MHC Class II<br>α<sub>1</sub>β<sub>1</sub>"] --- ag2[peptide]
end
subgraph cd4["CD4+ T cell"]
direction TB
c4[CD4] --- tr2[TCR]
end
ag2 --- tr2
m2l ----- c4
subgraph ac[All cells]
direction LR
m1l["MHC Class I<br>α<sub>3</sub>β<sub>2</sub>MG"] --- m1u["MHC Class I<br>α<sub>1</sub>α<sub>2</sub>"] --- ag1[peptide]
end
subgraph cd8["CD8+ T cell"]
direction TB
c8[CD8] --- tr1[TCR]
end
ag1 --- tr1
m1l ----- c8
}}
{|class="wikitable"
|-
!class
!genetic loci
!expression
!domains
!TCR on T cell
!binding cleft
|-
!MHC Class I
|
*HLA-A
*HLA-B
*HLA-C
|
*all nucleated cells
|α<sub>1</sub>, α<sub>2</sub><br>
''―――''<br>
β<sub>2</sub>MG, α<sub>3</sub>
|
*TCR+'''CD8''' on '''target cells'''
*'''CD8''' binds to α<sub>3</sub>
|peptide with 8-9 AAs
|-
!MHC Class II
|
*HLA-DP
*HLA-DQ
*HLA-DR
|
*dendritic cell
*macrophage
*B cell
*activated T cell
*some epitherial cells in thymus and intestine
|α<sub>1</sub>, β<sub>1</sub><br>
''―――''<br>
α<sub>2</sub>, β<sub>2</sub>
|
*TCR+'''CD4''' on '''antigen presenting cell'''
*'''CD4''' binds to β<sub>2</sub>
|peptide with 18-20 AAs
|-
!MHC Class III
|}
==T cell development==
#'''Prothymocytes''' migrate from bone marrow to thymus
#Prothymocytes proliferate and become '''Thymocytes''' in thymus
#Thymocytes express all of '''CD3''', '''CD4''' and '''CD8''' ('''Double positive thymocytes''')
#DP thymocytes are challenged to bind peptide-MHC ('''Positive selection''')
#CD8+ thymocytes are to suppress CD4 expression, vise versa ('''Single positive CD8 or CD4 cells''')
#SP cells encounter '''Epitherial reticular cells''' (APC - DC, Macrophage) and challenged to bind too efficiently to pMHC I or pMHC II (Negative selection)
#SP cells which do not bind too efficiently to pMHC I or pMHC II exit thymus as '''(naive) T cells'''
==T cell activation by 2 signaling (2 signal model)==
*Naive T cell needs doubled signals of '''TCR-pMHC interaction''' and '''co-stimulatory molecules''' by APC to be activated
*Co-stimulatory molecules: CD28, ICOS, CTLA-4 and PD-1
:#'''CD28''' and '''ICOS''' on T cell acts as '''activation signal'''
:#'''CTLA-4''' and '''PD-1''' on T cell acts as '''inhibitory signal''' against activation
==CD8+ T cell functions==
*Cytotoxicity
**Killing virus-infected cells, malignant cells
:#Perforin/granzyme-mediated
:#Fas/Fas ligand-mediated
*IFN-γ production
==CD4+ T cell differentiation==
{{#mermaid:
flowchart LR
APC --"PAMPs on APC"--> naive[Naive CD4+ T cell]
naive -.differentiate.-> Th1 -.T-bet.-> ifn["IFN-γ"] --> p1([IntraCellular pathogens])
naive -.differentiate.-> Th2 -.GATA-3.-> IL-4 --> p2([Helminths])
naive -.differentiate.-> Th17 -."RORγτ".-> IL-17 --> p3([ExtraCellular bacteria])
naive -..differentiate.-> Tfh* -.Bcl-6.-> IL-21 --> ab([Antibody production])
}}
:::::<nowiki>*</nowiki>Tfh = follicular B helper T cell
===Th1 differentiation===
{{#mermaid:
flowchart LR
NK -.-> ifn1["IFN-γ"] --> naive
APC --"PAMPs on APC"--> naive[Naive CD4+ T cell] --> Th1 -.T-bet.-> ifn2["IFN-γ"] --> ma[activates Macrophage<br>for killing] --> p1([IntraCellular pathogens])
ifn2 --> Th1
APC -.-> IL-12 --> naive
Th2 -.-> IL-4 --x naive
}}
===Th2 differentiation===
{{#mermaid:
flowchart LR
NK -.-> i41[IL-4] --> naive
APC --"PAMPs on APC"---> naive[Naive CD4+ T cell] --> Th2 -.GATA-3.-> IL-4,13 --> ma[activates Macrophage<br>for tissue repair]
Th2 -.GATA-3.-> i42[IL-4] --> b[activates B cells] -.-> ig[IgE, IgG4] --> mc([Mast cell degranuation])
Th2 -.GATA-3.-> IL-5 --> e[activates Eosinophils] ---> h([helminths])
Th1 -.-> ifn1["IFN-γ"] --x naive
Th1 -.-> IL-12 --x naive
}}
===Th17 differentiation===
{{#mermaid:
flowchart LR
APC --"PAMPs on APC"--> naive[Naive CD4+ T cell] --> Th17 -."RORγτ".-> IL-17 --> nt[recruite Neutrophil] --> ep([ExtraCellular pathogens])
}}
==MHC = HLA==
*Major Histocompatibility Complex (MHC) is rephrased as Human Leukocyte Antigen (HLA)
*Genetic loci are on 6th chromosome
==MHC and T cell receptor (TCR)==
*MHC presents peptide antigen and TCR recognize it
*'''CD8''' acts as co-receptor to '''MHC Class I''' on all '''target''' cells
*'''CD4''' acts as co-receptor to '''MHC Class II''' on '''antigen-presenting''' cells
{{#mermaid:
flowchart LR
subgraph ap[Antigen presenting cells]
direction LR
m2l["MHC Class II<br>α<sub>2</sub>β<sub>2</sub>"] --- m2u["MHC Class II<br>α<sub>1</sub>β<sub>1</sub>"] --- ag2[peptide]
end
subgraph cd4["CD4+ T cell"]
direction TB
c4[CD4] --- tr2[TCR]
end
ag2 --- tr2
m2l ----- c4
subgraph ac[All cells]
direction LR
m1l["MHC Class I<br>α<sub>3</sub>β<sub>2</sub>MG"] --- m1u["MHC Class I<br>α<sub>1</sub>α<sub>2</sub>"] --- ag1[peptide]
end
subgraph cd8["CD8+ T cell"]
direction TB
c8[CD8] --- tr1[TCR]
end
ag1 --- tr1
m1l ----- c8
}}
{|class="wikitable"
|-
!class
!genetic loci
!expression
!domains
!TCR on T cell
!binding cleft
|-
!MHC Class I
|
*HLA-A
*HLA-B
*HLA-C
|
*all nucleated cells
|α<sub>1</sub>, α<sub>2</sub><br>
''―――''<br>
β<sub>2</sub>MG, α<sub>3</sub>
|
*TCR+'''CD8''' on '''target cells'''
*'''CD8''' binds to α<sub>3</sub>
|peptide with 8-9 AAs
|-
!MHC Class II
|
*HLA-DP
*HLA-DQ
*HLA-DR
|
*dendritic cell
*macrophage
*B cell
*activated T cell
*some epitherial cells in thymus and intestine
|α<sub>1</sub>, β<sub>1</sub><br>
''―――''<br>
α<sub>2</sub>, β<sub>2</sub>
|
*TCR+'''CD4''' on '''antigen presenting cell'''
*'''CD4''' binds to β<sub>2</sub>
|peptide with 18-20 AAs
|-
!MHC Class III
|}
==T cell development==
#'''Prothymocytes''' migrate from bone marrow to thymus
#Prothymocytes proliferate and become '''Thymocytes''' in thymus
#Thymocytes express all of '''CD3''', '''CD4''' and '''CD8''' ('''Double positive thymocytes''')
#DP thymocytes are challenged to bind peptide-MHC ('''Positive selection''')
#CD8+ thymocytes are to suppress CD4 expression, vise versa ('''Single positive CD8 or CD4 cells''')
#SP cells encounter '''Epitherial reticular cells''' (APC - DC, Macrophage) and challenged to bind too efficiently to pMHC I or pMHC II (Negative selection)
#SP cells which do not bind too efficiently to pMHC I or pMHC II exit thymus as '''(naive) T cells'''
==T cell activation by 2 signaling (2 signal model)==
*Naive T cell needs doubled signals of '''TCR-pMHC interaction''' and '''co-stimulatory molecules''' by APC to be activated
*Co-stimulatory molecules: CD28, ICOS, CTLA-4 and PD-1
:#'''CD28''' and '''ICOS''' on T cell acts as '''activation signal'''
:#'''CTLA-4''' and '''PD-1''' on T cell acts as '''inhibitory signal''' against activation
==CD8+ T cell functions==
*Cytotoxicity
**Killing virus-infected cells, malignant cells
:#Perforin/granzyme-mediated
:#Fas/Fas ligand-mediated
*IFN-γ production
==CD4+ T cell differentiation==
{{#mermaid:
flowchart LR
APC --"PAMPs on APC"--> naive[Naive CD4+ T cell]
naive -.differentiate.-> Th1 -.T-bet.-> ifn["IFN-γ"] --> p1([IntraCellular pathogens])
naive -.differentiate.-> Th2 -.GATA-3.-> IL-4 --> p2([Helminths])
naive -.differentiate.-> Th17 -."RORγτ".-> IL-17 --> p3([ExtraCellular bacteria])
naive -..differentiate.-> Tfh* -.Bcl-6.-> IL-21 --> ab([Antibody production])
}}
:::::<nowiki>*</nowiki>Tfh = follicular B helper T cell
===Th1 differentiation===
{{#mermaid:
flowchart LR
NK -.-> ifn1["IFN-γ"] --> naive
APC --"PAMPs on APC"--> naive[Naive CD4+ T cell] --> Th1 -.T-bet.-> ifn2["IFN-γ"] --> ma[activates Macrophage<br>for killing] --> p1([IntraCellular pathogens])
ifn2 --> Th1
APC -.-> IL-12 --> naive
Th2 -.-> IL-4 --x naive
}}
===Th2 differentiation===
{{#mermaid:
flowchart LR
NK -.-> i41[IL-4] --> naive
APC --"PAMPs on APC"---> naive[Naive CD4+ T cell] --> Th2 -.GATA-3.-> IL-4,13 --> ma[activates Macrophage<br>for tissue repair]
Th2 -.GATA-3.-> i42[IL-4] --> b[activates B cells] -.-> ig[IgE, IgG4] --> mc([Mast cell degranuation])
Th2 -.GATA-3.-> IL-5 --> e[activates Eosinophils] ---> h([helminths])
Th1 -.-> ifn1["IFN-γ"] --x naive
Th1 -.-> IL-12 --x naive
}}
===Th17 differentiation===
{{#mermaid:
flowchart LR
APC --"PAMPs on APC"--> naive[Naive CD4+ T cell] --> Th17 -."RORγτ".-> IL-17 --> nt[recruite Neutrophil] --> ep([ExtraCellular pathogens])
}}
