Actors involved
Mechanism
Where?
Antigen presentation via Class I HLA molecules
By all nucleated cells, as well as platelets.
Antigen presentation via Class II HLA molecules
- in the basal state, only by professional antigen-presenting cells, i.e. dendritic cells, macrophages, and B cells;
They are also present on the surface of thymic epithelial cells - in states of cellular stress (particularly in the context of transplantation), other cells can express Class II HLA molecules, such as endothelial cells and T cells.
When?
Antigen presentation via Class I HLA molecules
Continuously, so that CD8+ T cells can recognise and then eliminate abnormal cells.
The activated CD8+ T cell acts as a “watchman” capable of verifying cell integrity via peptides presented by Class I HLA molecules.
If the cell is normal , it will only synthesize normal proteins, recognised as “self” that do not activate the CD8+ T cell.
If the cell is abnormal ,it will synthesise abnormal proteins recognised as “non-self” by the CD8+ T cell, which will activate and exert its cytotoxic functions towards the abnormal cell.
Antigen presentation via Class II HLA molecules
Continuously for professional antigen-presenting cells and thymic epithelial cells.
Only in an inflammatory context for other cells.
How is this done?
After priming of peptides
Priming is the set of stages of degradation of a protein antigen, obligatory and prior to the embedding of the peptide in the groove of the HLA molecule.
Priming and antigen presentation of Class I HLA molecules1% of all proteins produced by the cell are permanently sent for degradation via ubiquitin marking. This marking sends them to the proteasome where they will undergo the action of enzymes cleaving them into smaller peptides. These then pass from the cytosol to the endoplasmic reticulum using TAP pumps. Once in the endoplasmic reticulum, they can undergo the action of other proteolytic enzymes. At the end of these degradation and cleavage processes, we obtain in the endoplasmic reticulum a pool of small peptides of a few amino acids, derived from endogenous proteins.
Ultimately, the peptides that can be embedded in a Class I HLA molecule are:
- Endogenous
“Endogenous” and “self” are not synonymous
A protein is said to be endogenous if it is synthesised by the cell that will present it. However, a cell can synthesise different “self” proteins in a non-physiological context (stress, particularly viral infection, malignant degeneration, etc.).
An endogenous protein synthesized by the body is therefore not necessarily “of itself”!
In contrast, all endogenous proteins (“self” and “non-self”) are presented vi Class I HLA molecules.
- Short
Mostly 9 amino acids , i.e., nonamers.
Once loaded with a peptide, Class I HLA molecules are expressed on the surface of all nucleated cells and platelets. Complexes [peptide - Class I HLA molecule] can interact with the TCR of CD8+ T cells and the KIRs of NK cells.
Class II HLA molecules are also present in the endoplasmic reticulum. In order to prevent endogenous peptides from embedding themselves, chaperone proteins (invariant Li chain) support Class II HLA molecules and congest their peptide groove until they reach the endosome and are loaded there with exogenous peptides.
The peptide pocket of Class II HLA molecules forming in the endoplasmic reticulum is protected by the invariant Li chain to prevent peptides present in the endoplasmic reticulum from becoming embedded there. As soon as the complex [Li chain – Class II HLA molecule] is formed, it is transported to the endosome. By carrying out its role of recycling exogenous and transmembrane proteins, the endosome becomes the loading site, into Class II HLA molecules, of peptides of 12 to 25 amino acids emanating from degradation by lysosomal enzymes. The invariant Li chain is also degraded to make room for the peptide.
The complex [peptide - Class II HLA molecule] is expressed, in the basal state, on the surface of dendritic cells, B cells, macrophages and thymic epithelial cells. During an inflammatory response, certain other cells (including endothelial cells and T cells) can also express Class II HLA molecules.
The particular case of cross-presentation carried out by the dendritic cellThe dendritic cell is the only one able to carry out cross-presentation, that is to say able to present peptides resulting from the degradation of exogenous proteins via Class I HLA molecules. It is a major characteristic of this cell, which makes it responsible for the link between innate immunity and adaptive immunity. Indeed, it is thanks to this cross-presentation that the dendritic ell can activate CD8+ T cells to induce a cellular reaction towards antigens not expressed in the dendritic cell.
Consequences
Unlike the B cell which recognises any native antigen thanks to its BCR, the T cell is incapable of recognizing a native antigen. The antigen priming and presentation mechanisms are therefore strictly obligatory: without them, none of the mechanisms in which T cells are involved could take place!
What needs to be remembered
| Nucleated cells & platelets | Dendritic cell | B cell | Macrophage | |
|---|---|---|---|---|
| HLA molecule expressed at basal state | Class I | Class IClass II | Class IClass II | Class IClass II |
| Origin of the peptide presented | endogenous | endogenous & exogenousexogenous | exogenous endogenous | exogenous endogenous |
| Interaction with T-cell TCR | CD8+ | CD8+CD4+ | CD8+CD4+ | CD8+CD4+ |
| Destruction of infected, abnormal cells | Thymic education of CD8+ T cellsThymic education of CD4+ T cells | Destruction of infected, abnormal B-cellsCD4+ T-cell/B-cell cooperation | Destruction of infected, abnormal macrophagesT-cell cooperation CD4+ (Th1)/macrophage in intracellular bacterial infections. (e.g., tuberculosis) | |
| Function of antigen presentation | Peripheral activation of CD8+ T cellsPeripheral activation of CD4+ T cells | |||
Destruction of infected, abnormal dendritic cells |