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The Host Response to Grafts and Transplantation Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Although first identified by transplantation reactions, the MHC antigens are now known to play key roles in an immune response. In both humans and mice, the MHC genes are organized into regions encoding three classes of molecules: Class I, Class II, and Class III (Figure 11.3). Class I and Class II molecules are the molecules which influence the response to transplanted tissues and are expressed as heterodimers on the cell surface. The various gene products encoded by the Class I and Class II genes are structurally and functionally homologous. The Class I molecules in the human are HLA-A, -B, and -C and H-2 K, D, and L in the mouse. The Class II molecules are HLA-DR, -DQ, and -DP in the human and I-A and I-E in the mouse. Class III genes encode different products including soluble complement components, steroid 21-hydroxylase enzymes, tumor necrosis factors (TNF), and heat shock proteins, which will not be discussed further in this section. There are still other genes within the MHC, including nonclassical Class I molecules, Class I and Class II pseudogenes, genes for chaparoning peptide loading (DM, DO), genes for the proteosome components (LMP), and the peptide transporters (TAP). Many of the molecules encoded by these genes also play roles in the immune response but are not considered histocompatibility antigens and will not be discussed in this chapter.
Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The ability of T cells to recognize antigens depends on their interaction with the Peptide-Major Histocompatibility Complex (pMHC). CD4+ T (Helper T/TH) cells recognize peptides presented by MHC Class II (MHC2) molecules, where the expression of MHC2 is typically limited to antigen-presenting cells. MHC2 can be aberrantly expressed on malignant cells, although MHC Class I (MHC1) molecules are expressed on all nucleated cells including malignant cells. CD8+ T cells (cytotoxic T cells/CTL) are responsible for recognizing peptides bound to MHC1 molecules.
Gene Therapy for Lung Cancer
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Choon Taek Lee, David P. Carbone
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.
Emergence of mRNA vaccines in the management of cancer
Published in Expert Review of Vaccines, 2023
Mohamad Irfan Mohamad Razif, Nabilah Nizar, Nur Hannah Zainal Abidin, Syasya Nasuha Muhammad Ali, Wan Nurul Najihah Wan Zarimi, Junaidi Khotib, Deny Susanti, Muhammad Taufiq Mohd Jailani, Muhammad Taher
The neoantigen’s immunogenicity is influenced by a number of different factors in addition to its structure. Neoantigens are acquired by antigen-presenting cells, such as dendritic cells and macrophages, after being released by cancer cells. The proteasome breaks down neoantigens into tiny peptides, which are then loaded onto major histocompatibility complex molecules and displayed on the surface of antigen presenting cells. Then, neoantigen-loaded antigen presenting cells go into lymph nodes that drain tumors. Specific T cells identify neoantigen-major histocompatibility complexes by T cell receptors when the proximity of antigen presenting cells and T cells is convenient for interaction. As a result, the spatial location of the antigen presenting cell is another critical factor.
Development of a nonhuman primate challenge model to evaluate CD8+ T cell responses to an adenovirus-based vaccine expressing SIV proteins upon repeat-dose treatment with checkpoint inhibitors
Published in mAbs, 2022
Richard Graveline, Morad Haida, Carolyne Dumont, Dominic Poulin, Florence Poitout-Belissent, Rana Samadfam, Sven Kronenberg, Franziska Regenass-Lechner, Rodney Prell, Marie-Soleil Piche
MHC genotyping was performed in this study to permit the characterization of the antigen-specific T-cell immune response by tetramer staining, ELIspot and cytolytic assays. These peptide-specific responses required MCMs to express the MHC Class I alleles Mafa-A1*063 with or without Mafa-B*104:01. If, however, the antigen-specific CD8+ T-cell immune response is not required, looking at the broad CD8 response will not need to identify animals carrying a specific MHC allele (Figure 10). As such, a basic study design could include cynomolgus monkeys from diverse origin in a study of at least 4-week duration with a single immunization. The parameters tested would be hematology, clinical chemistry/CRP, immunophenotyping (excluding Tetramer staining), and ELIspot assay with an overlapping peptide pool covering the entire Nef sequence. Alternatively, hexon peptides could be used in place of a Nef peptide pool, as long as NHPs only show a basal level of response during predose.
Dendritic cell vaccine as a potential strategy to end the COVID-19 pandemic. Why should it be Ex Vivo?
Published in Expert Review of Vaccines, 2022
Jonny Jonny, Terawan Agus Putranto, Enda Cindylosa Sitepu, Raoulian Irfon
Antigens presented by MHC-I triggers CD8 + T cell response, while antigens presented by MHC-II triggers CD4 + T cell response. CD8 + T cells primarily kill host cells infected with viruses. Therefore, most CD8+ will proliferate during acute viral infections after exposure to antigens presented by DCs to assist viral clearance [56]. Meanwhile, CD4 + T cells differentiate into various sub-types depending on the cytokines (e.g. Th1, Th2, Tfh, and Th17) [57]. Each sub-types has a specific function in mediating humoral and cellular adaptive immunity. Moreover, after interaction with DCs, some T cells differentiate into T memory cells [52]. DCs are also essential in germinal center (GC) development by facilitating T cell follicular helper (Tfh) differentiation and directly migrating to the light zone of GC [58].