Definition of an Allergen (Immunobiology)
Richard F. Lockey, Dennis K. Ledford in Allergens and Allergen Immunotherapy, 2014
In addition to the thymus-dependent and thymus-independent classes of antigens, a third antigen class exists, termed “superantigens.” A “superantigen” is an antigen capable of triggering nonspecific activation of many T cells, leading to wide antibody response. These are proteins produced by many pathogens, including bacteria, mycoplasma, and viruses, which can bind to the variable region of the beta chain (V-beta) of the T-cell receptor and cross link it to MHC class II molecules on the surface of antigen-presenting cells. Superantigens function as intact molecules; unlike classic antigens, they are not processed and presented by antigen-presenting cells. The extent of T-cell stimulation is a function of the frequency of T cells bearing V-beta regions that can bind a specific superantigen. There has been some speculation about the superantigenic nature of some allergic responses [40].
Pathogenicity and Virulence
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Superantigens are composed of a group of bacterial and viral proteins that can form a direct bridge between antigen presenting cells and T cells by binding directly first to MHC Class II molecules and then to T cell receptors bearing a specific subset of V beta chains. Antigens that are conventionally processed and presented will interact with about one in 10,000 T cells, but superantigens bypass this procedure and can stimulate up to twenty percent of the T cell population. This excessive T cell response results in the production and release into the bloodstream of massive quantities of IL-2 and other proinflammatory cytokines, which can lead to shock and death of the host. Included in this group are the enterotoxin of Staphylococcus, the exfoliative toxins, the toxins of Toxic Shock Syndrome, and also the pyogenic toxins of both staphylococci and streptococci. It is thought that tissue destruction resulting from the inflammation induced by these superantigens enables the bacteria to multiply to greater numbers and to be more easily spread.
Role of Bacteria in Blood Infections
K. Balamurugan, U. Prithika in Pocket Guide to Bacterial Infections, 2019
Superantigens are extracellular protein toxins released by gram-positive bacteria in the blood that are pyrogenic, increase host susceptibility to endotoxic shock, suppress immunoglobulin production, and have mitogenic activity for specific T-cell subset (Curtis, 1996; Commons et al., 2008). This produces an extensive release of proinflammatory cytokines with massive immune activation. These superantigens are likely to be involved in the pathogenesis of various invasive infections. A total of 11 superantigens have been identified so far, including streptococcal pyrogenic exotoxin (spe) A, C, G, H, I, J, K, L, M, streptococcal mitogenic exotoxin (sme) Z, and streptococcal superantigen (ssa) (Commons et al., 2008). Except speG, speJ, and smeZ, all of the superantigens-encoding genes are associated with bacteriophages (Ferretti et al., 2001; Proft & Fraser, 2003; Proft et al., 2003). S. aureus strains secrete around 24 superantigens, which involved in antiphagocytic activity and establishment of toxic shock syndrome Type-1 (Spaulding et al., 2013).
The Immunologic Profiles of Kawasaki Disease Triggered by Mycoplasma pneumoniae Infection
Published in Fetal and Pediatric Pathology, 2023
Hong-bo Hu, Xiao-peng Shang, Jian-gang Wu, Ya-ling Cai
Children with KD often experience the abnormal activation of T cells during the disease period, resulting in the abnormal activation of the immune system and causing clinical syndromes. This is the key step and initial link of the activation of the immune system in KD [19,20]. It has been demonstrated that the number of CD4+T cells and the CD4/CD8 ratio were increased, while the number of CD8+T lymphocytes was reduced in patients with KD [10,21]. In the present study, the CD4/CD8 ratio of MP-KD was higher than that of KD. It is hypothesized that the presence of vasculitis in KD may be triggered by an immune response to a superantigen from an infectious pathogen in those who are genetically susceptible [5, 7]. Mycoplasma arthritidis has been shown to produce a superantigen, implying that other Mycoplasma species, such as MP, may do the same [22,23]. Superantigens are polyclonal CD4+ T lymphocyte stimulators that cause massive cytokine production [24]. There is also some evidence that both Th1 and Th2 cytokines may be activated during the acute state of KD [25]. As a result, interacting directly with class II major histocompatibility complex molecules, MP superantigens activate polyclonal CD4+ T lymphocytes, resulting in a massive release of cytokines that cause vascular inflammation [5,7,26].
Acute abdomen: a rare presentation of group a streptococcal infection
Published in Acta Chirurgica Belgica, 2023
Jelle Lubach, Marie Vannijvel, Hendrik Stragier, Yves Debaveye, Albert Wolthuis
Exotoxins produced by S. pyogenes can act as superantigens. These can directly activate up to 20% of circulating T cells, causing a massive cytokine release [14]. Considering that the underlying mechanism of TSLS is hypercytokinemia induced by superantigens derived from GAS, cytokine absorption therapies might be useful. Using intravenous polyspecific immunoglobulin G (IVIG) in necrotising soft tissue infections is lacking evidence for improving patient outcomes and reducing mortality [15,16]. A trial of Darenberg et al. [17] using IVIG as adjunctive therapy in streptococcal toxic shock syndrome (STSS) showed a higher mortality in the placebo group, but this showed not to be significant possibly due to the small patient group used in this study. They did show a decrease in sepsis-related organ failure assessment score in the IVIG group. These results are similar to a prospective study of Carapetis et al. [18].
Relevance of glycans in the interaction between T lymphocyte and the antigen presenting cell
Published in International Reviews of Immunology, 2021
Wilton Gómez-Henao, Eda Patricia Tenorio, Francisco Raúl Chávez Sanchez, Miguel Cuéllar Mendoza, Ricardo Lascurain Ledezma, Edgar Zenteno
MHC molecules have been widely described as being involved in the development, maturation, and thymic selection of T cells, in antigenic presentation and the activation of T lymphocytes with superantigens and used as a strategy in immunotherapy. Experimental models showed that mutations on αAsn78 or αAsn118 in MHC II affect antigenic presentation, but only the absence of αAsn118 induces a decrease in T cells during positive selection [100]. This agrees with structural analyses showing that the N-glycans in αAsn78 and βAsn19 are found near the antigen-binding groove in MHC II, but αAsn118 is located near the cell surface, suggesting that the N-glycans in αAsn78 and βAsn19 are related to the stability of the interaction of the pMHC II complex whereas αAsn118 is related to stabilizing the MHC II structure. Accordingly, experimental evidence showed that mutation of αAsn78 and βAsn19 or N-glycan elimination can positively or negatively affect MHC II’s ability to bind and present antigens and also affect the interaction with the TCR [105, 106], These findings demonstrate how glycosylation influences antigenic presentation, modulating the interaction and formation of the pMHC II complex, however, the absence of N-glycans does not affect the assembly of MHC II [105–107].
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