INTERAZIONI ED ORIENTAMENTO TRA TCR E MHC · Ag Binding to Ab on B cell & ... l’attecchimento o il rigetto dei trapianti QuickTime™ and a TIFF (Uncompressed) decompressor are

INTERAZIONI ED ORIENTAMENTO TRA TCR

E MHC

Annual Review of Biophysics and Biomolecular Structure

l 31 121 149

CO-RECEPTORS

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TCR CO-RECEPTOR RECOGNITION

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T cells• T cell receptors (TCR) – Ag specific• Glycoproteins CD4 (helper T cells) or CD8

(cytotoxic T cells)

CD4 T cell or helper T cell

CD8 T cell or cytotoxic T cell

CD4 CD8

TCR TCR

CD4+ T cells• Helper T cells − involved in Ab production• Recognition of “exogenous Ag”

– Bacteria– Extracellular Ag

• Recognize MHC class II molecule– Present on “antigen presenting cells” = APC– e.g. Macrophages, Dendritic Cells, B cells

APC = e.g., Macrophage

TCR

PeptideAntigen

CD4 T Cell

MHCClass II CD4

TCR Recognizes its Epitope Only in the Context of MHC• CD4 TCR – peptide/MHC Class

II• CD8 TCR – peptide/MHC Class I

APC

TCR

PeptideAntigen

CD4 T Cell

MHCClass II CD4

Cytokines

Y YY

Ag Binding to Ab on B cell & Cytokines from T cells Activates B cell•Proliferates•Undergoes “Class-switch”•Becomes Plasma Cells that secretes Ab•Leads to formation of Memory B cells•Increased affinity of Ab produced

Activation of CD4 Helper T Cell

T Cell is Activated•Proliferates•Produces Cytokines

Y

Cytokines Activate Macrophages

- Boost PerformanceBacteria

Cytokines

PeptideTCR

MHCClass II

CD4

APC

Cytokines

B Cells are Antigen Presenting Cells (APC) too

CD4 T cell

B cell

Major Histocompatibility Complex

THE MHC IN MOUSE AND HUMAN

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The mouse haplotypes



Codominanza del sistema MHC



L’ MHC determina l’attecchimento o il rigetto dei

trapianti



Codominanza e ricombinazione creano nuovi

haplotipi





Prima dei Transgenici:Congenic mice



Genetic differences between congenic mice



The MHC-I /II Structure



MHC Structure



Differenze tra Molecole MHC-I / MHC-II



Differenze tra molecole MHC-I e MHC-II





MHC genes



Peptide presentation MHC-I



Peptide presentation MHC-II





The peptide



THE EFFECT OF PEPTIDE LOADING



Kb conformationalPeptide induced changes

Peptide presentation requirement



La conformazione del peptide



Il Polimorfismo HLA



Il polimorfismo HLA



The H-2 chromosome organization



The MHC haplotypes on the cell surface





Gruppo 3

• Ljunggren HG, Stam NJ, Ohlen C, Neefjes JJ, Hoglund P, Heemels MT, Bastin J, Schumacher TN, Townsend A, Karre K, et al. Empty MHC class I molecules come out in the cold. Nature. 1990 Aug 2;346(6283):476-80.

La restrizione immune





Il processamento dell antigene



Differente Processing degli Ag intra ed extra cellulari



Ubiquitinazione degli Ag



Dal citoplasma al RER



APC cells



MHC-I presentation pathway



MHC-II presentation pathway



MHC-II presentation pathway



MHC-II



MHC-II presenting peptide



CD1 present lipid antigens



Documents

INTERAZIONI ED ORIENTAMENTO TRA TCR E MHC · Ag Binding to Ab on B cell & ... l’attecchimento o il rigetto dei trapianti QuickTime™ and a TIFF (Uncompressed) decompressor are