Antigen
Antigens can be classified:
According to their nature
Antigens can be protein, polysaccharide, lipid, or a mix of several types (for example a glycosylated protein). In practice, it is important to make the dichotomy between peptide antigens and others. This distinction is important because TCRs (on the surface of T cells) can only recognise protein antigens after priming – i.e., cleavage into small peptides of 9 amino acids for Class I, or 15 to 21 amino acids for Class II – while membrane immunoglobulins (BCRs) or soluble immunoglobulins (antibodies) can recognise antigens of all natures.
According to their persistence after denaturation
The molecules of the organism adopt a tertiary structure, that is to say that the peptide chain is organized in space to form a 3D structure defining, for example, domains of activity (for example: folding to form a catalytic site).
Under certain conditions (variation in temperature, acidity, oxidative stress, etc.), this conformation is broken and the peptide chain loses its 3D conformation and becomes linearised again.
We therefore distinguish between:
- conformational antigens: they are composed of motifs that are not contiguous in the molecular sequence but close in the 3D structure.
- linear antigens: they are composed of contiguous motifs in the molecular sequence.
When the 3D structure is broken, the conformational antigen is lost but the linear antigen persists.
Since the antigens recognised by the TCR are processed, TCRs only recognise linear antigens (not conformational antigens).
BCRs can recognise conformational and linear antigens.
According to their source
- Microbial antigens: coming from microorganisms (bacteria, viruses, fungi, etc.).
- Allergens: substances in the environment that cause allergies (hypersensitivities).
- Alloantigens: coming from organisms of the same species but characteristics of subgroups of individuals within a given species (HLA molecules, ABO system, etc.).
- Xenoantigens: coming from organisms of different species (specific glycosylation of horse immunoglobulins for example, etc.).
- Autoantigens: Substances in self (individual) that become antigens, as in autoimmune diseases.
We speak of exogenous and endogenous antigen to the antigen-presenting cell:
- exogenous, which comes from outside the cell.
- endogenous, which comes from inside the cell.
Do not confuse endogenous antigen and autoantigen:
- an endogenous antigen can be of viral origin,
- an exogenous antigen can be an autoantigen (e.g., insulin).
Concept of epitope
An epitope is the smallest portion of the antigen recognised by an immunoreceptor. It is a very short molecular sequence, the one that is recognised by the paratope of adaptive immunity immunoreceptors (TCR and/or BCR).
Cross-reactivity
Since immunoreceptors recognize epitopes that are very small motifs within complex molecules, there may be epitope redundancy within very different molecules.
This is particularly evident in cases of cross allergies, for example between kiwi and latex.
In transplantation in particular, there may be anti-HLA immunisation against HLA molecules that have never been encountered by the recipient. Most often, it is an anti-HLA immunisation against a molecularly close molecule which crosses with another HLA molecule.
The proximity between two HLA molecules can be quantified by the epitope difference between the two molecules.
Antigen immunogenicity criteria
We distinguish between the concepts of antigenicity and immunogenicity.
Antigenicity is the ability of the antigen to bind to an immunoreceptor. Immunogenicity is the ability of an antigen to generate an adaptive immune response. In other words, not all antigens are immunogenic.
A certain number of parameters are correlated with the immunogenicity of an antigen:
- size: the larger the antigen, the more immunogenic it is.
- complexity: the more complex the antigen, the more immunogenic it is.
- the number of epitopes: the more epitopes the antigen has, the more immunogenic it is.
- the difference from self: the more the antigen is different from self, the more immunogenic it is.
- accessibility: the more the antigen is in contact with antigen-presenting cells, the more immunogenic it is.
What needs to be remembered
Antigen is a molecular structure recognised by immunoreceptors. Depending on its characteristics, antigen may be more or less immunogenic. For transplantation, it is important to understand the concept of epitope and cross-reactivity: this explains why we can be immunised (have already produced antibodies) directed against molecules close to those already encountered. This is why it is essential to rigorously follow the anti-HLA immunisation of future organ recipients!
