The Host Response to Grafts and Transplantation Immunology
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
The tissue or histocompatibility antigens which cause vigorous rejection responses and are the primary obstacle to transplantation are encoded within the Major Histocompatibility Complex, or MHC (Figure 11.3). In the human, the MHC encodes the so-called HLA or Human Leukocyte Antigens, while in the mouse it encodes a similar set of molecules called H-2 or Histocompatibility-Locus 2 antigens. All vertebrates studied to date possess a major histocompatibility complex. In the mouse, the MHC is found on chromosome 17 while in the human, it is found on chromosome 6. There are also weaker histocompatibility antigens that cause milder rejection responses. In both species, the weaker histocompatibility antigens are encoded at many different chromosomal sites and are collectively called minor histocompatibility antigens.
Monoclonal Antibodies
Thomas F. Kresina in Monoclonal Antibodies, Cytokines, and Arthritis, 2020
The emergence of considerable information concerning the stuctures involved in antigen recognition by T cells provides a useful framework for designing disease-specific therapeutic interventions. Administration of MAbs targeted against disease-related MHC alleles or TCR V region determinants has proven useful in ameliorating several autoimmune diseases in animal models, probably by virtue of interrupting T cell recognition events critical to the pathogenesis of these diseases. Progress in the identification of disease-related MHC alleles in human autoimmune disease should facilitate the development of potentially efficacious MAbs directed against these molecules. Gaps exist in our knowledge concerning the antigen(s) responsible for perpetuating human autoimmune diseases and the TCR V region structures employed in the recognition of these antigens; nonetheless, continued progress in the elucidation of disease-related TCR V region structures coupled with increasingly detailed knowledge of the configuration of disease-related MHC antigen binding clefts should facilitate construction of MAbs directed against these structures. The future availability of MAbs that bind disease-specific T cell recognition structures should ultimately provide a useful adjunct in the therapy of autoimmune diseases.
Disease Prediction and Drug Development
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam in Introduction to Computational Health Informatics, 2019
The Major-Histocompatibility-Complex (MHC) is a large class of the gene-family involved in the immune system. The proteins encoded by MHC-complex are known as MHC-proteins and play a major role in antigen-binding. The antigens first bind to MHC-proteins, and then are recognized by T-cell receptors that activate the T-cells cloning, and leads to an immune system response. MHC molecules are two types: MHC I and MHC II. MHC I binds peptides in a narrow range length; MHC II allows a binding for varied length usually between 9 and 25 residues. There is a segment of nine amino-acid long essential for MHC binding to antigens. The prediction of these nine amino-acids is based upon deriving the amino-acid segments with strong binding affinity and is approximated using many artificial intelligence techniques such as neural networks, ant-colony optimization (metaheuristic search), iterative learning, clustering using microarray data and particle-swarm optimization (metaheuristic search). Binding-affinity should be strong for the proper immune-system activation.
Lessons from transmissible cancers for immunotherapy and transplant
Published in Immunological Medicine, 2022
Rafael Cardoso Maciel Costa Silva, Carolina Panis, Bruno Ricardo Barreto Pires
Tumor transplantation studies paved the way for an increased understanding of major histocompatibility complex (MHC) biology [1]. At that time, the mechanisms that governed tissue rejection (and, in this case, cancer rejection as well) were not established. Currently, many advances have allowed us to better comprehend these mechanisms, many of which are also significant barriers to a possible cancer transmission through allogeneic responses. The immune response against foreign cells that express different MHCs repertoires (allorecognition) is the main driver of tissue rejection [2]. The MHC codes for critical polygenic and polymorphic molecules (evaluated before transplant donor selection) involved with antigen presentation to T cells. MHC type I molecules (MHC-I), usually expressed by all nucleated cells within vertebrates, interact with T cell receptors (TCRs) from CD8+ T cells, mainly responsible for cytotoxic adaptive immune responses. MHC type II (MHC-II), expressed mainly by professional antigen presenting cells, such as dendritic cells (DCs) and activated macrophages, interact with TCRs from CD4+ T cells that are responsible for ‘helper’ adaptive immune responses, ‘orchestrating’ different aspects of cellular and humoral immunity. Foreign MHCs are very important to tissue rejection and, as discussed in this review, transmissible cancer immune response.
Advances in viral oncolytics for treatment of multiple myeloma – a focused review
Published in Expert Review of Hematology, 2021
Ayesha Sarwar, Laila Hashim, Muhammad Salman Faisal, Mobeen Zaka Haider, Zahoor Ahmed, Tehniat Faraz Ahmed, Moazzam Shahzad, Iqraa Ansar, Sundas Ali, Muhammad Muaaz Aslam, Faiz Anwer
The tumor associated antigens are expressed by various tumor cells. These are presented in the class I major histocompatibility complex (MHC) molecules to be processed by antigen-presenting cells (APC) which in turn present them in class II MHC. These MHC molecules presented by the APCs and the tumor cells are recognized by the circulating naïve T cells. This leads to the generation of cytotoxic CD8 + T lymphocytes colonies that have the ability to destroy the tumor tissue. Adoptive cell transfer therapy involves removing the tumor antigen-specific cytotoxic T cells and multiplying them in colonies ex-vivo. They can then be infused back into the patient [102]. A study by Cole et al [88] has demonstrated that tumor antigen-specific T cells can be utilized in the delivery of oncolytic viruses to the tumor. However, a problem arises in few tumors without the expression of enough tumor-specific antigen.
HLA transgenic mice: application in reproducing idiosyncratic drug toxicity
Published in Drug Metabolism Reviews, 2020
Takeshi Susukida, Shigeki Aoki, Tomohiro Shirayanagi, Yushiro Yamada, Saki Kuwahara, Kousei Ito
Human leukocyte antigens (HLAs) are essential molecules ubiquitously expressed throughout the body. They are responsible for regulating the adaptive immune response by communicating with CD4+ or CD8+ T cells using peptide fragments that identify molecules as self or non-self (i.e. abnormal). HLAs can be roughly divided into 2 classes: class I molecules present endogenously processed peptides that target CD8+ T cells, while class II molecules are expressed on the surface of antigen-presenting cells, such as dendritic cells, macrophages, and B cells, which target CD4+ T cells (Redwood et al. 2018). HLA-mediated T cell activation is intended to protect our body from foreign substances, such as viruses, bacteria, drugs, and graft cells; however, excessive immune responses, represented as hypersensitivity reactions and autoimmune diseases, can severely damage organs. For example, the major histocompatibility complex (MHC) is associated with an autoimmune disease comprising HLA-B27 and ankylosing spondylitis, which was discovered in patients (Brewerton et al. 1973). Although this landmark observation provided beneficial insights into understanding onset risk, the fundamental mechanism of this association remained undetermined. Thus, researchers aimed to develop a novel approach to clarify the role of HLA molecules in autoimmune diseases.
Related Knowledge Centers
- Adaptive Immune System
- Protein
- White Blood Cell
- Autoimmune Disease
- T Cell
- Antigen
- Locus
- Gene Polymorphism
- Cell
- Organ Transplantation