Antigen

Immunological name for any substance to which antibodies and certain lymphocyte receptors (TCRs) can specifically bind (antigen-antibody reaction). This process is an essential part of adaptive immunity against pathogens.

Antigens are able to trigger an immune response. They therefore have an immunogenic effect. The site of the antigen that is recognized by the corresponding antibody is called the epitope.

Basically one can distinguish:

• foreign antigens, glycoproteins of another living being
• Self-antigens, glycoproteins of the own body

Most antigens are proteins; however, carbohydrates, lipids or other substances can also be effective antigenically.

Protein antigens are recognized either by antibodies or by T-cell receptors (TCR). It was fundamentally important to realize that T lymphocytes, by means of their antigen-specific receptors, only recognize protein antigens when they are expressed via an antigen-MHC complex on the surface of antigen-presenting cells (APC). Endogenous substances can also act as antigens and thus induce "autoantibodies". S.a.u. Autoimmune disease, see also special features of activation by superantigens.

The antigen processing of the MHC class I pathway, takes place in several steps, which, via protein splitting in the proteasome, a processing by a transporter protein(TAP) to a peptide loading complex, ultimately leads to the loading of the MHC molecule and finally to the antigen presentation on the cell surface of the APC.

The antigen processing of the MHC class II pathway (exogenous antigens taken up by APCs by phagocytosis, endocytosis or macrophinocytosis) also proceeds in several steps. The antigens are processed by various methods. The antigens are bound by different receptors (B-cell antigen receptor, Fc-receptor, C-type lectin receptor, etc.), internalised, degraded in enzyme-rich vesicles, translocated into the cytosol and finally introduced into the MHC class I pathway (so-called cross-presentation).

In contrast to peptide antigens, lipid antigens are not recognized by certain cells in conjunction with the MHC complex, but with CD1 molecules. This CD1-dependent presentation pathway plays a special role especially in the skin.

Small molecules (<5kD) such as individual carbohydrates, amino or fatty acids or certain drugs cannot cause an immune reaction.

Various low-molecular substances only trigger an immune reaction when they bind to a carrier protein. This means that a non-immunogenic protein becomes an immunogen with a new epitope to induce an immune response. They are called haptens.

The benefit of antigen recognition by lymphocytes is that the organism is able to recognise foreign substances against which it has no hereditarily coded receptors. Lymphocytes that bind to endogenous substances (autoantigens) die, lymphocytes that bind to foreign antigens trigger the adaptive immune response.

Antigen-presenting cells (APCs) are specialized cells of the immune system that present antigens to T cells. These include dendritic cells, macrophages and B cells. APCs take up substances by endocytosis, process them in the endosomes and couple them to MHC molecules, which in turn are presented on the cell surface. A T cell with a suitable T cell receptor (TCR) can then recognise the antigen as foreign.

B lymphocytes (B cells) that have bound to an antigen with their B cell receptor (the membrane-bound precursor of the antibody) are activated either directly (TI antigen) or with the help of a T helper cell, depending on the antigen. T-helper cells that have bound to an antigen-MHC complex and recognised the antigen as foreign secrete cytokines. These cytokines stimulate B cells (plasma cells) to produce specific antibodies (IgG, IgE, IgA). Antibodies bind specifically to the antigen, mark it with it (opsonation) and thus lead to its phagocytosis by macrophages. The macrophages bind to the constant region of the antibodies with their Fc receptors.

Allergens that can cause allergies are called antigens. They are caused by an excessive immune response (allergy) to an intrinsically harmless allergen.

Due to the physicochemical properties of the allergenic substance, a sensitization to the substance or to the substance bound to a carrier occurs when the substance is disposed of accordingly.
T-helper cells play a key role in the immune system. Depending on the type of contact with the allergen, they differentiate into two different types:

• When macrophages present the antigen, TH1 cells are formed which produce class G immunoglobulins.
• If B lymphocytes or dendritic cells present the allergen, TH2 cells are formed in the case of a genetic allergic predisposition, which are responsible for the production of IgE. The specific IgE attaches itself to the mast cells concentrated in the skin and mucous membranes and stimulates them to release mediators, i.e. pro-inflammatory substances such as histamine, when the allergen is encountered again. At the same time the allergen activates the specific TH2 cells. The stimulated TH2 cells additionally intensify the allergic symptoms by sensitising the mast cells via cytokines, activating eosinophils, stimulating the expression of adhesion molecules and suppressing the formation of TH1 cells.

Allergens have different epitopes for IgE and TH cells.
The IgE-forming B lymphocytes and TH cells react with different regions of the allergenic molecules, the B and T cell epitopes. B-lymphocytes bind with their immunoglobulin receptors preferably to surface structures of the native allergen molecules. These B-cell epitopes are determined by the characteristic spatial structure of the native allergens and are often composed of unconnected peptide segments. Such B-cell epitopes are discontinuous and conformation dependent. However, in order for a B lymphocyte activated by B cell epitopes to produce IgE antibodies, it needs further signals from an allergen-specific TH2 cell. The TH cells do not react with the intact allergen, but with allergenic fragments, which in addition must be bound to the body's own MHC molecules of class II of antigen-presenting cells (APC). To do this, the allergens would have to be taken up by the APC and degraded to peptides of 10-35 amino acids. These T-cell epitopes depend on the sequence of the amino acids and not on the conformation of the native allergen.
The switch of the B-lymphocyte to the synthesis of IgE antibodies is controlled by the cytokines interleukin-4 and interleukin-13 of the activated TH2 cell as well as by direct contact of certain cell membrane molecules.