In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
In biochemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology. Protein phosphorylation often activates many enzymes.
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.
T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.
The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumor formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors. Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR.
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-antigen interactions.
In academia, computational immunology is a field of science that encompasses high-throughput genomic and bioinformatics approaches to immunology. The field's main aim is to convert immunological data into computational problems, solve these problems using mathematical and computational approaches and then convert these results into immunologically meaningful interpretations.
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:
Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ἕρπειν, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. As of 2020, 115 species are recognized, all but one of which are in one of the three subfamilies. Herpesviruses can cause both latent and lytic infections.
Molecular mimicry is the theoretical possibility that sequence similarities between foreign and self-peptides are enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. Despite the prevalence of several peptide sequences which can be both foreign and self in nature, just a few crucial residues can activate a single antibody or TCR. This highlights the importance of structural homology in the theory of molecular mimicry. Upon activation, these "peptide mimic" specific T or B cells can cross-react with self-epitopes, thus leading to tissue pathology (autoimmunity). Molecular mimicry is one of several ways in which autoimmunity can be evoked. A molecular mimicking event is more than an epiphenomenon despite its low probability, and these events have serious implications in the onset of many human autoimmune disorders.
Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment can be recognized by a T-cell receptor. Specifically, the fragment, bound to the major histocompatibility complex (MHC), is transported to the surface of the antigen-presenting cell, a process known as presentation. If there has been an infection with viruses or bacteria, the antigen-presenting cell will present an endogenous or exogenous peptide fragment derived from the antigen by MHC molecules. There are two types of MHC molecules which differ in the behaviour of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can only recognize tens to hundreds of copies of a unique sequence of a single peptide among thousands of other peptides presented on the same cell, because an MHC molecule in one cell can bind to quite a large range of peptides. Predicting which antigens will be presented to the immune system by a certain MHC/HLA type is difficult, but the technology involved is improving.
Phosphoproteomics is a branch of proteomics that identifies, catalogs, and characterizes proteins containing a phosphate group as a posttranslational modification. Phosphorylation is a key reversible modification that regulates protein function, subcellular localization, complex formation, degradation of proteins and therefore cell signaling networks. With all of these modification results, it is estimated that between 30–65% of all proteins may be phosphorylated, some multiple times. Based on statistical estimates from many datasets, 230,000, 156,000 and 40,000 phosphorylation sites should exist in human, mouse, and yeast, respectively.
An immunoreceptor tyrosine-based inhibitory motif (ITIM), is a conserved sequence of amino acids that is found intracellularly in the cytoplasmic domains of many inhibitory receptors of the non-catalytic tyrosine-phosphorylated receptor family found on immune cells. These immune cells include T cells, B cells, NK cells, dendritic cells, macrophages and mast cells. ITIMs have similar structures of S/I/V/LxYxxI/V/L, where x is any amino acid, Y is a tyrosine residue that can be phosphorylated, S is the amino acid serine, I is the amino acid isoleucine, and V is the amino acid valine. ITIMs recruit SH2 domain-containing phosphatases, which inhibit cellular activation. ITIM-containing receptors often serve to target immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors, resulting in an innate inhibition mechanism within cells. ITIM bearing receptors have important role in regulation of immune system allowing negative regulation at different levels of the immune response.
Minor histocompatibility antigen are peptides presented on the cellular surface of donated organs that are known to give an immunological response in some organ transplants. They cause problems of rejection less frequently than those of the major histocompatibility complex (MHC). Minor histocompatibility antigens (MiHAs) are diverse, short segments of proteins and are referred to as peptides. These peptides are normally around 9-12 amino acids in length and are bound to both the major histocompatibility complex (MHC) class I and class II proteins. Peptide sequences can differ among individuals and these differences arise from SNPs in the coding region of genes, gene deletions, frameshift mutations, or insertions. About a third of the characterized MiHAs come from the Y chromosome. Prior to becoming a short peptide sequence, the proteins expressed by these polymorphic or diverse genes need to be digested in the proteasome into shorter peptides. These endogenous or self peptides are then transported into the endoplasmic reticulum with a peptide transporter pump called TAP where they encounter and bind to the MHC class I molecule. This contrasts with MHC class II molecules's antigens which are peptides derived from phagocytosis/endocytosis and molecular degradation of non-self entities' proteins, usually by antigen-presenting cells. MiHA antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells.
S-arrestin is a protein that in humans is encoded by the SAG gene.
Protein phosphorylation is a reversible post-translational modification of proteins in which an amino acid residue is phosphorylated by a protein kinase by the addition of a covalently bound phosphate group. Phosphorylation alters the structural conformation of a protein, causing it to become activated, deactivated, or otherwise modifying its function. Approximately 13,000 human proteins have sites that are phosphorylated.
