TCR (T Cell Receptor) or co-stimulatory molecule interactions with APC receptors are disrupted or prevented by biotechnology-derived immunotherapeutic drugs. In this diagram, monoclonal antibodies and fusion proteins that stop T cells from activating are displayed given below figure.
![Biologic Reagents That Block Interactions between T Cells and Antigen-Presenting Cells](https://pharmacygyan.com/wp-content/uploads/2021/09/Biologic-Reagents-That-Block-Interactions-between-T-Cells-and-Antigen-Presenting-Cells.png)
Table of Contents
Blockade of T Cell Receptor Interactions
Monoclonal antibodies made in the lab (muromomab, teplizumab, and visilizumab) bind to CD3 on activated T cells. Blocking antibodies inhibit CD3 from interacting with class I or II molecules, which can lead to recipient graft rejection and, in rare circumstances, the graft rejecting the host.
Blockade of Co-Stimulatory Molecule Interactions
Biotechnology-derived fusion proteins or monoclonal antibodies can inhibit the interaction between co-stimulatory factors on T cells and APCs. Two genes are fused in the lab and put into an expression vector, such as a bacterium or yeast, to make a fusion protein. The active parts of both proteins are combined in the fusion protein when it is translated. Currently, two fusion proteins are utilized to prevent T cells and APCs from interacting with co-stimulator molecules.
Abatacept is a co-stimulator inhibitor in a new class of drugs called disease-modifying antirheumatic drugs (DMARDs). In patients with rheumatoid arthritis, T cell activation is the major cause of the inflammatory response in the synovium. Abatacept consists of an Fc region from the immunoglobulin G (IgG) antibody and the extracellular domain of CTLA-4. The CTLA-4 fusion protein physically blocks the interaction between CD28 and the B7 on APCs. Failure to engage CD28 drives activated T cells into apoptosis.
Alefacept is another fusion protein indicated for psoriasis Vulgaris, an autoimmune skin disease. Activated CD4, CD8, and memory cells are found in skin lesions. Alefacept prevents T cell activation and reduces the severity of the lesions. The fusion protein consists of LFA-3 (CD58) linked to the distal end of an antibody molecule. Interactions between the soluble alefacept and the T cell CD2 molecule block the binding of CD2 to the CD58 on APCs.
Monoclonal antibodies, which inhibit co-stimulatory molecules, are also indicated for the treatment of psoriasis. For example, efalizumab blocks interactions between the CD11a component of LFA-1 and the adhesion factors on APCs. Again, downregulation of T cells reduces the severity of skin lesions.
Aberrant interactions between tcr and class ii molecules
Superantigens
Superantigens are molecules that activate up to 20% of all T lymphocytes (typical antigen response stimulates just 0.01 percent of T cells), causing them to produce large amounts of proinflammatory cytokines like tumour factor– (TNF-). TNF- causes life-threatening hypovolemic shock and organ failure when released into the bloodstream.
Superantigens work in a unique way to activate CD4 cells. The bridging of the constant area of class II molecules and the variable portions of the TCR-chain (V) brings T cells and APCs into close contact. Superantigen binding, on the other hand, is distinct in because it takes place outside of the usual binding clef showing in below figure.
![Aberrant interactions between tcr and class ii molecules](https://pharmacygyan.com/wp-content/uploads/2021/09/Aberrant-interactions-between-tcr-and-class-ii-molecules-min-1.png)
Staphylococcal and streptococcal superantigens have been implicated in food poisoning, exfoliative dermatitis in infants (scalded skin syndrome), cellulitis, scarlet fever, and toxic shock syndrome. Staphylococcus aureus secretes five entero[1]toxins (SEA, SEB, SEC2, SEE, and TSST-1). Enterotoxins are similar to exotoxins but usually only cause moderate to severe diarrhea. All staphylococcal enterotoxins can cause the symp[1]toms of food poisoning, but only SEA and SEB are involved in exfoliative dermatitis. Toxic shock syndrome is associated with the TSST-1, SEB, or SEC2 superantigens. In the last 20 years, an increase has been seen in the inci[1]dence of streptococcal toxic shock syndrome associated with necrotizing fasciitis or myositis. The etiologic agents are invasive Group A streptococcal strains such as Streptococcus pyogenes. These strains produce three different superantigens (SPE-A, SPE-B, and SPE-C) and numerous pyogenic toxins. SPE-A is specifically associated with streptococcal toxic shock syndrome (sTSS). Streptococcal and staphylococcal superan[1]tigens act in a similar manner.
Make sure check our amazing article related to this post: Surface Interactions Between T Cells and Antigen-Presenting Cells