China
Africa
Explore chapters and articles related to this topic
Adaptive immune response: Antigens, lymphocytes, and accessory cells
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, John W. Sleasman
The sequence of events leading to antigen processing and presentation in a dendritic cell starts by endocytosis of antigens on membrane patches, transport to an acidic compartment (lysosome) within the cell that allows antigen degradation into small peptides. As antigens are broken down, vesicles coated with newly synthesized HLA-II molecules fuse with the lysosome. Some of the peptides generated during processing have high affinity for the binding site located within the MHC-II heterodimer that is initially occupied by an endogenous peptide (class II–associated invariant chain peptide [CLIP]), displaced by the antigen-derived peptide. The resulting MHC-peptide complexes are then transported to the APC cell membrane where they can interact with and activate CD4+ T cells bearing receptors specific for the peptide.
Active Specific Immunization by the Use of Leukemic Dendritic Cell Vaccines
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Ilse Houtenbos, Gert J. Ossenkoppele, Arjan A. van de Loosdrecht
AML blasts consistently show a high expression of MHC class I molecules whereas MHC class II molecules are variably expressed (35,36). The role of MHC class II molecules to present tumor antigens to CD4-positive Th cells to obtain antitumor T-cell responses is well established (37). Antigen presentation via the MHC class II pathway is severely hampered by the presence of class II-associated invariant chain peptide (CLIP) in the antigen-binding groove. CLIP is a small remnant of the invariant chain that serves a chaperone for newly synthesized class II molecules and prevents unwanted antigens from binding in the endoplasmic reticulum (38). CLIP is released upon replacement by the antigen. A high amount of CLIP expressed on AML blasts might serve as a tumor escape mechanism and results in a shortened disease-free survival of AML patients (35).
Human Blood Dendritic Cells
Published in Brian J. Nickoloff, Dermal Immune System, 2019
Peter S. Freudenthal, Gary S. Wood
Human blood dendritic cells express high levels of HLA-A, -B, and -C surface markers, collectively known as MHC class I antigens. In addition, isolated dendritic cells that have been in culture for at least 36 h over the course of the isolation protocol express much higher levels of MHC class II markers than any other cell type as yet isolated from blood. By fluorescence-activated cell sorting (FACS) analysis, several studies have shown that dendritic cells fluorescently label with 1 to 2 logs higher intensity for HLA-DR, -DP, and -DQ markers than do either monocytes, B cells, B lymphoblasts, or T lymphoblasts.7,18,19 This helps to explain the observed potency of dendritic cells as antigen-presenting cells. Another significant, although unusual, marker found on the surface of isolated dendritic cells is the MHC class II invariant chain.7 The invariant chain has been shown to increase the efficiency of antigen-presenting function.20
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).
AE37: a HER2-targeted vaccine for the prevention of breast cancer recurrence
Published in Expert Opinion on Investigational Drugs, 2021
Patrick M. McCarthy, G. Travis Clifton, Timothy J. Vreeland, Alexandra M. Adams, Anne E. O’Shea, George E. Peoples
While initial work on the G89 peptide was conducted, the Ii-Key peptide was also being developed. The Ii-Key peptide is a portion of the MHC Class II invariant chain (Ii), a protein that typically binds the MHC Class II complex while in the endoplasmic reticulum to prevent the binding of endogenous protein as is intended for MHC Class I. The Ii protein stays in place throughout transport to the trans face of the Golgi apparatus where MHC Class II is charged with exogenous protein by HLA-DM [24]. Only a small portion of the Ii protein regulates the size of the MHC Class II binding site named hIi(77–92) or ‘Ii-Key’ [25]. Additional reduction of this protein to identify the minimal active sequence showed that the ‘core’ segment of the Ii protein (LRMKLPK) holds the MHC protein binding groove (PBG) open by binding to an allosteric site [26]. Even a reduction of this Ii-Key core segment to aa77-80 (LRMK) retained over 50% of the activity of its larger, complete core segment [27].
Hydroxychloroquine: a comprehensive review and its controversial role in coronavirus disease 2019
Published in Annals of Medicine, 2021
Pankaj Bansal, Amandeep Goyal, Austin Cusick, Shubham Lahan, Harpal S. Dhaliwal, Poonam Bhyan, Pradnya Brijmohan Bhattad, Fawad Aslam, Sagar Ranka, Tarun Dalia, Lovely Chhabra, Devang Sanghavi, Bhavin Sonani, John M. Davis
Being lipophilic, HCQ easily permeates cell membranes and accumulates in intracellular vesicles, including lysosomes, endosomes, and autophagosomes. In these acidic vesicles, it interferes with vesicular enzyme functionality (such as proteases) by increasing the pH [25]. In antigen-presenting cells (APCs), HCQ interferes with the processing of antigens to peptides, thereby preventing peptide presentation for MHC-II [1,26]. Furthermore, in the loading compartment of MHC-II-containing acidic endosomes, HCQ possibly interferes with the interaction of peptides with MHC-II. A crucial step in this interaction is the clipping of the MHC-II invariant chain and replacement by antigen peptides, which forms the MHC-II/peptide complex. An increase in pH caused by HCQ inhibits invariant chain clipping by proteases. This selectively inhibits the binding of low-affinity self-antigen peptides to the MHC-II binding site but not of high-affinity foreign-antigen peptides (such as bacterial peptides), possibly explaining why HCQ is not associated with an increased infection risk [1,21] (Figure 2).