Gene Therapy for Lung Cancer
Kenneth L. Brigham in Gene Therapy for Diseases of the Lung, 2020
The MHC is a region of highly polymorphic genes whose products are expressed on the surface of most cells. MHC class I molecules bind endogenously synthesized peptide fragments and present them on cell surface for recognition by the T-cell receptor (TCR) on CD8+ T cells. MHC class II molecules are primarily expressed on “professional antigen-presenting cells” such as macrophages and dendritic cells that are thought to be primarily responsible for binding peptide fragments derived from extracellular proteins and presenting them to T helper cells. This interaction induces the production of cytokines necessary for the expansion of cytotoxic effectors. MHC molecules therefore play a key role in all phases of the immune response. Tumor cells usually have some level of expression of MHC class I molecules on their surface, but in many tumor cells expression of MHC may be low.
Genetics of Endocrine Disorders and Diabetes Mellitus
George H. Gass, Harold M. Kaplan in Handbook of Endocrinology, 2020
The earliest associations of IDDM susceptibility were with the class I MHC alleles B8 and B15.2–4 Further work has shown more significant associations with certain class II MHC alleles. The MHC class I antigens (HLA-A, -B, and -C) contain a cytoplasmic domain, a transmembrane domain, and three extracellular domains. Two of the extracellelar domains combine to form a groove in which an antigen-derived peptide is held for presentation to T-cell receptors of cytotoxic (CD8+) T-lymphocytes. MHC class I antigens are found on the surface of all nucleated cells. The MHC class II antigens are composed of an α and a β chain, each encoded by a separate gene in the DP, DQ, or DR region of the MHC. The two chains form a structure analagous to the class I molecule, with an antigen-presenting groove composed of parts of both chains. The class II antigens are expressed on the surface of macrophages, B lymphocytes, T helper lymphocytes, monocytes, and some epithelial cells. When a foreign antigen is endocytosed by an antigen-presenting cell, the foreign antigen is partially degraded and presented on the surface of the antigen-presenting cell in the antigen binding groove of an MHC molecule. The MHC class II molecule with the foreign antigen then associates with a T-cell receptor of T helper (CD4+) lymphocytes, triggering the immune response to the foreign antigen.
Basic science
Declan Costello, Guri Sandhu in Practical Laryngology, 2015
The other unique feature of laryngeal mucosa is the presence of MHC class II molecules, which are involved in presenting an exogenous antigen to T helper cells. MHC class II molecules are typically expressed only on ‘professional’ antigen presenting cells such as dendritic cells and macrophages. While this expression has been shown in the laryngeal mucosa of healthy individuals, in-vitro grown laryngeal epithelial cells do not express MHC class II molecules unless they are stimulated with interferon-gamma (IFN-γ). The mechanism of in-vivo stimulation and the role of MHC class II expression, however, are not fully understood. It is believed that these molecules contribute to immune tolerance to inhaled antigens in the absence of co-stimulatory molecules, although this remains largely speculative.
Low abundance members of the gut microbiome exhibit high immunogenicity
Published in Gut Microbes, 2022
Geongoo Han, Hien Luong, Shipra Vaishnava
MHC class II is an essential part of exogenous antigen presentation to the CD4+ T cell and is mainly expressed on professional antigen-presenting cells (APCs) but also on intestinal epithelial cells (IECs).22,23 Several components participate in the MHC class II antigen presentation pathway and the expression of those components is regulated by CIITA in the nucleus. Invariant chain, also known as CD74, stabilizes the MHC class II complex and mediates the assembly and trafficking of that complex.23 To assess whether the presence of low abundance bacteria affects the MHC class II antigen presentation, we compared normalized counts of genes that are related to MHC class II, and several important genes for the expression of MHC class II were significantly higher in the undiluted than the diluted group (Figure 5a). To assess the effects of low abundance bacteria on MHC class II expression at the protein level, we stained the small intestine with the MHC class II marker (I-A/I-E). In the Und, there were more MHC class II molecules than the Dil after a week of colonization (p = .002), and most of them were only present in the crypts (Figure 5b and 5c). After five weeks of treatment, however, there was no difference in MHC class II molecules between the two groups (p = .122), and those molecules were substantially expressed not only in the crypts but also in the villi (Fig. S8).
MAPPs for the identification of immunogenic hotspots of biotherapeutics; an overview of the technology and its application to the biopharmaceutical arena
Published in Expert Review of Proteomics, 2018
Valerie Quarmby, Qui T Phung, Jennie R Lill
These tools use primary amino acid sequence data and, therefore, do not take into account higher order structure, the effect of posttranslational modifications and/or non-sequence related factors such as formulation, or the presence of process-related impurities or product related variants in a drug product. This also limits their ability to assess epitope presentation from biotherapeutic formats that have conjugated moieties such as antibody–drug conjugates or pegylation (a protocol being employed to expand upon the in vivo stability, or higher dynamic range of certain biotherapeutics). In addition, these are tools to decipher if an MHC class II molecule can be presented on the cell surface, which does directly correlate with its ability to induce an immunogenic response. The same is true for MAPPs and other methods based upon presented peptides, presentation does not necessarily correlate with immunogenicity; however, a peptide cannot be immunogenic if it is not presented via MHC II to a CD4+ T cell.
Soluble immune checkpoints and T-cell subsets in blood as biomarkers for resistance to immunotherapy in melanoma patients
Published in OncoImmunology, 2021
Devayani Machiraju, Melanie Wiecken, Nina Lang, Ingrid Hülsmeyer, Jasmin Roth, Timo E. Schank, Rosa Eurich, Niels Halama, Alexander Enk, Jessica C. Hassel
The role of soluble immune checkpoints is an active area of research. The major sources of sLAG3 in the blood are dendritic cells and B cells.22 In vitro, sLAG3 enhances the expansion of melanoma-specific CD8 + T lymphocytes23 and, in contrast, is known to impair monocyte differentiation resulting in reduced immunostimulatory capacities.24 In MHC II expressing melanoma cells, the addition of sLAG3 protects tumor cells from FAS mediated and drug-induced apoptosis.25 In line with this observation, we found increased sLAG3 concentrations in nonresponding patients to anti-PD1 therapy. However, we observed a positive association of sLAG3 with the number of regulatory T cells (CD3+ CD4+ CD25+ CD127-) in the peripheral blood. The mechanism through which sLAG3 is involved in resistance to anti-PD1 therapy particularly remains unclear. It might influence the interaction between MHC class II expressing dendritic cells and T cell activation.
Related Knowledge Centers
- B Cell
- Major Histocompatibility Complex
- Mhc Class I
- Peptide
- Thymus
- Endothelium
- Dendritic Cell
- Monocyte
- Antigen
- Immune Response