antigen

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Antigen Dr.Gogoi University of Fiji

Calibri:

Immunogen, antigen, epitope, hapten Immunogen: a stimulus that produces a humoral or cell-mediated immune response Antigen: any substance that binds specifically to an antibody or a T-cell receptor

Symbol:

Immunogen, antigen, epitope, hapten All immunogens are antigens but not all antigens are immunogens Some very small molecules called haptens can bind to Ab’s or TCR’s but they cannot initiate an immune response…

Default Design:

Immunogen, antigen, epitope, hapten Immunogen: a stimulus that produces a humoral or cell-mediated immune response Antigen: any substance that binds specifically to an antibody or a T-cell receptor Epitope: the portion of an antigen that is recognized and bound by an Ab or TCR/MHC complex ( aka antigenic determinant ) Hapten: a low molecular weight molecule that can be made immunogenic by conjugation to a suitable carrier

Antigen:

Immunogen, antigen, epitope, hapten Paratope… Paratope: “The site in the variable (V) domain of an antibody or T-cell receptor that binds to an epitope on an antigen

Immunogen, antigen, epitope, hapten:

The key event…

Immunogen, antigen, epitope, hapten:

The basis of immunogenicity… Foreignness Molecular size Chemical composition and heterogeneity Degradability

Immunogen, antigen, epitope, hapten:

The basis of immunogenicity… Foreignness Molecular size Chemical composition and heterogeneity Degradability

The key event…:

Presentation of processed antigen…

The basis of immunogenicity…:

There are two general classes of antigens Exogenous ( external ) Endogenous ( internal )

PowerPoint Presentation:

There are two general classes of antigens Exogenous: presented by A ntigen P resenting C ells (APC’s). These are macrophages, B-cells, and some dendritic cells Endogenous: typically peptides derived from any protein; an infected cell displays “not-self” proteins and is, thus, an “altered self cell”

The basis of immunogenicity…:

There are two general classes of antigens Exogenous: these antigens are presented in MHC-II; they are seen by T-cells with a TCR and an associated protein called CD4 Endogenous: these antigens are presented by MHC-I; they are seen by T-cells with a TCR and an associated protein called CD8

Presentation of processed antigen…:

There are two classes of T-cells T H have CD4 which interacts with MHC-II; thus, CD4 + T-cells are “MHC-II restricted.” T H cells are “helper cells” that send signals ( via cytokines and surface proteins ) to other cells of the immune system. The T H cells function as the “brain” of the immune system.

There are two general classes of antigens:

There are two classes of T-cells T C have CD8 which interacts with MHC-I; thus, CD8 + T-cells are “MHC-I restricted.” T C cells become cytotoxic T lymphocytes (CTL’s) which attack “altered self-cells ( e. g., infected cells.) “Altered self-cells” are also called “target cells.” They are the targets for the CTL’s cytotoxicity.

There are two general classes of antigens:

Experimental systems… viz. “haptens” Hapten: a low molecular-weight molecule that can be made immunogenic by conjugation to a suitable carrier…

There are two general classes of antigens:

Haptens…

There are two classes of T-cells:

Haptens…

There are two classes of T-cells:

Antigen Processing

Experimental systems… viz. “haptens”:

T cells do not recognise native antigens Y Y B Y Y Y Y Y Y Y B Y T Y T Proliferation and antibody production No proliferation No cytokine release Cross-linking of surface membrane Ig Y B Y B Y B Y B Y B Y B Y B

Haptens…:

Cell surface peptides of Ag Antigens must be processed in order to be recognised by T cells Y T T cell r esponse No T cell response No T cell response No T cell response No T cell response Soluble native Ag Cell surface native Ag Soluble peptides of Ag Cell surface peptides of Ag presented by cells that express MHC antigens ANTIGEN PROCESSING

Haptens…:

M  M  Early evidence that antigens are catabolised M  Macrophages and radiolabelled Listeria monocytogenes Internalisation Rapid binding to cell surface M  Degradation of bacteria and release of Radiolabelled protein into supernatant and cells

PowerPoint Presentation:

M  M  M  M  0mins 60mins T Listeria -specific T cells The interaction of T cells with macrophages requires antigen catabolism Listeria NO T CELLS BIND NO T CELLS BIND T CELLS BIND Listeria coated plastic NO T CELLS BIND NO T CELLS BIND T cell do not bind stably to antigen presenting cells unless the antigen is catabolised

PowerPoint Presentation:

Only metabolically active cells can process antigen Determinants recognised by T cells are generated by catabolic activity that is dependent upon the viability of macrophages Fix with paraformaldehyde or poison with sodium azide M  Pulse with Listeria for 60min & wash cells M  Add Listeria specific T cells M  T Listeria -specific T cells NO T CELLS BIND Antigen presenting cells must be viable to PROCESS antigen

PowerPoint Presentation:

M  M  M  M  M  M  Listeria Listeria Where does antigen processing take place? M  M  Incubate with CHLOROQUINE T Add Listeria specific T cells T CELLS BIND NO T CELLS BIND Chloroquine inhibits lysosomal function (a lysosomotrophic drug) Antigen processing involves the lysosomal system

PowerPoint Presentation:

What form of antigen is produced by antigen processing? T Ovalbumin specific T cell line Catabolism reduces antigens to peptides that can be recognised by T cells APC Viable APC Viable T T T T T T T T T T T T T T T T Digested ovalbumin Fixed APC Fixed APC Native ovalbumin Ag APC T cell response

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