Immunology chapter 5, sections 5-6 through 5-21, and 5-23
bare lymphocyte syndrome type I or MHC I deficiency
rare genetically determined immunodeficiency disease in which MHC class I molecules are not present on cell surfaces, as a result of non functional TAP proteins. The result is a deficiency of CD8 T cell function.
professional antigen presenting cells
refers primarily to dendritic cells, but also to macrophages and B cells, all of which take up, process and present antigens from the environment, and once activated, are able to activate naive or partly activated T cells
HLA-E
relatively invariant human MHC class I molecules that form ligands for NK cell receptors
HLA-G
relatively invariant human MHC class I molecules that form ligands for NK cell receptors
present
MHC molecule does this to the peptide antigen to the T cell receptor
gene families
set of genes encoding proteins of similar structure, and often of similar function, such as the MHC class I genes
calreticulin
soluble chaperone protein in the endoplasmic reticulum that is part of the peptide-loading complex that loads peptides onto MHC class I molecules in the endoplasmic reticulum
alloreactive T cells
T cell in one member of a species that responds to an allogenic antigen from another member of the same species
tapasin
TAP associated protein, a chaperone protein involved in the assembly of peptide: MHC class I molecule complexes in the endoplasmic reticulum
promiscuous binding specificity (promiscuous specificity)
the ability of a protein to bind a number of different ligands; an example of this is the MHC molecules, which can each bind numerous peptides of different sequences
isotypes
the class of an immunoglobulin-that is, IgM, IgG, IgD, IgA, or IgE-each of which has a distinct heavy chain constant region encoded by a different constant region gene. The heavy chain constant region determines the effector properties of each antibody class.
HLA type
the combination of HLA class I and class II allotypes that person expresses
peptide-binding motif
the combination of anchor residues in an MHC protein that correspond to the amino acid sequences of peptides that can bind to that protein
antigen presentation
the display of antigen as peptide fragments bound to MHC molecules on the surface of cells. This is the form in which antigen is recognized by α:β T cells
antigen processing
the intracellular degradation of proteins into peptides that bind to MHC molecules for presentation to α:β T cells
HLA class I molecules
the name for the human version of an MHC class I molecule
HLA class II molecules
the name for the human version of an MHC class II molecule
human leukocyte antigen complex (HLA complex)
the name for the major histocompatibility complex in humans. It is loacted on the short arm of chromosome 6 and encodes the polymorphic HLA class I and class II molecules, as well as other proteins involved in immune system function. Individual genes are designated by capital letters, such as HLA-A, and alleles are designated by numbers, such as HLA-A*0201.
class I region
the part of the major histocompatibility complex that contains the MHC class I heavy chain genes
class II region
the part of the major histocompatibility complex that contains the MHC class II alpha and beta chain genes
MHC restriction
the property that a given T cell receptor recognizes its peptide antigen only when the peptide is bound to a particular form of MHC molecule
class III region or central MHC
the region of the major histocompatibility complex between the class I and II regions. It contains no genes for class I or II MHC molecules
peptide editing
the selection of peptides by the peptide loading complex that bind strongly to MHC class I molecules, together with the trimming of bound peptides to the correct length by the endoplasmic reticulum aminopeptidase
constitutive proteasome
the version of the proteasome present in normal uninfected cells
MHC class II
a family of molecules normally found only on antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. The antigens presented by these peptides are derived from extracellular proteins ; hence, the (this)-dependent pathway of antigen presentation is called the endocytic or exogenous pathway
antigen-presenting cell
a heterogeneous group of immune cells that mediate the cellular immune response by processing and presenting antigens for recognition by certain lymphocytes such as T cells. Classical APCs include dendritic cells, macrophages, Langerhans cells and B cells.
HLA-A
a highly polymorphic human MHC class I gene
HLA-B
a highly polymorphic human MHC class I gene
HLA-C
a highly polymorphic human MHC class I gene
HLA-F
a monomorphic human MHC class I molecule that is a chaperone for HLA class I molecules that lose their bound peptide at the cell surface
allotypes
a naturally occurring variant of a protein. These are encoded by different alleles of the same gene.
peptide-loading complex
a protein complex in the endoplasmic reticulum membrane that loads peptides from the TAP transporter onto MHC class I molecules
HLA-DO
a relatively invariant human MHC class II molecule. The function of this is to counteract that of HLA-DM
MHC class II transactivator (CIITA)
a transcriptional activator of MHC class II genes. If defective, it results in the absence of MHC class II molecules on all cells, causing a severe immunodeficiency characterized by a lack of CD4-T cell function
CD8
a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).
ERp57
thiol reductase protein that is part of the peptide loading complex that loads peptides onto MHC class I molecules in the endoplasmic reticulum
MIIC (MHC Class II compartment)
acronym for MHC class II compartment and pronounced 'em two see". an endosomal compartment in professional antigen presenting cells where MHC class II molecules load with peptides derived from pathogens and antigens that have been taken up from the extracellular environment
alloreaction
adaptive immune response made by one member of a species to an allogeneic antigen from another member of the same species
anchor residues
amino acid residues in MHC binding peptides that interact with pockets in the peptide binding groove of the MHC molecule. Peptides that bind to a given MHC allotype have the same or similar of these
HLA-DM
an invariant MHC class II molecule in humans that is involved in the intracellular loading of MHC class II molecules with peptides
alloantibody
antibody that is made by immunization of one member of a vertebrate species with antigen derived from another member of the same species. Alloantibodies recognize antigens that are the result of allelic variation of polymorphic genes. Common types of alloantibody are those recognizing blood group antigens, and MHC class I and class II molecules
self peptides
any peptide produced from the body's own proteins. in the absence of infection, these peptides occupy the peptide binding sites of MHC molecules on cell surfaces and are usually not recognized as antigenic by that person's immune system
non-self peptides
any peptide that derives from a protein not present in a person's own body. It can refer to a peptide derived from a pathogen protein or from a protein from a genetically unrelated person. such peptides are recognized as foreign and provoke an immune response
self proteins
any protein of a person's own body. these proteins are usually not recognized as antigenic by that person's immune system
non-self proteins
any protein that is not present in a person's own body. It can refer to a pathogen protein or to a protein from a genetically unrelated person that is recognized as foreign. Such proteins are recognized as foreign and provoke an immune response.
homozygous
describes an individual who has inherited the same form (allele) of a given gene from both parents
autologous
describes cells, HLA molecules, and other components, that derive from the individual or person in question
highly polymorphic
describes genes that have many alleles and for which most individuals in a population are heterozygous
oligomorphic
describes genes that have only a small number of different alleles in the population
heterozygous
describes individuals who have inherited different forms (alleles) of a given gene from their two parents
allogenic
describes two members of the same species who are genetically different
T-cell co-receptors
either of the cell surface glycoproteins CD4 or CD8, which cooperate with the T cell receptor to determine which target cells a given T cell will interact with
endoplasmic reticulum aminopeptidase (ERAP)
enzyme in the endoplasmic reticulum that removes amino acids from the amino-terminal end of peptides bound to MHC class I molecules to improve their fit, a process known as peptide editing
helper T cell
general name for effector CD4 T cells that function to help other immune system cells perform their roles, such as to help B cells produce antibody
isoform
general term for a particular MHC protein
monomorphic
having only one form. the term is used, for example, for genes that have only one allele
haplotype
in reference to a linked cluster of polymorphic genes, the set of alleles carried on a single chromosome. Every person inherits two (usually different) haplotypes for such genes, one from each parent. The term was first used in connection with the genes of the major histocompatibility complex
cross-priming
initiation of an adaptive immune response by cross presentation of antigen
β2-microglobulin
invariant polypetide that is common to all MHC class I molecules. Also called the light chain of MHC class I molecules
major histocompatibility complex molecules (MHC molecules)
large cluster of mainly immune-system genes present in all vertebrates that encodes, among other proteins, the highly polymorphic MHC class I and class II molecules, which present peptide antigens to T cells and are the basis of an individual's tissue type
proteasome
large multisubunit protease present in the cytoplasm of all cells that degrades cytoplasmic proteins. It generates the peptides presented by MHC class I molecules
cytotoxic T cell
type of effector T cell that kills its target cells. It expresses the CD8 co receptor and recognizes peptide antigens presented by MHC I molecules. It is important in host defense against viruses and other cytosolic pathogens because it can recognize and kill the infected cells
genetic polymorphism
variation in a population owing to the existence of two or more alleles of a given gene
calnexin
membrane protein of the endoplasmic reticulum that facilitates the folding of newly synthesized MHC molecules and other glycoproteins
self-MHC
A person's own MHC class I and class II molecules
immunoproteasome
A proteasome assembled using alternative β form subunits in response to pro-inflammatory signals.
transporter associated with antigen processing (TAP)
ATP binding protein in the endoplasmic reticulum membrane that transports peptides from the cytosol to the lumen of the ER. It is composed of two subunits, TAP-1 and TAP-2. It supplies MHC class I molecules with peptides
HLA-DP
one of the highly polymorphic human MHC class II molecules. Each class II molecule is made from alpha and beta chains encoded by A and B genes, respectively.
HLA-DQ
one of the highly polymorphic human MHC class II molecules. Each class II molecule is made from alpha and beta chains encoded by A and B genes, respectively.
HLA-DR
one of the highly polymorphic human MHC class II molecules. Each class II molecule is made from alpha and beta chains encoded by A and B genes, respectively.
MHC class I
one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the body. Their function is to display peptide fragments of non-self proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because these molecules present peptides derived from cytosolic proteins, the pathway of its presentation is often called cytosolic or endogenous pathway
class II associated invariant chain peptide (CLIP)
peptide of variable length cleaved from the invariant chain protein by proteases in the endosomal pathway. CLIP remains unstably bound in the peptide binding cleft of an MHC class II molecule until it is removed by the HLA DM protein and replaced by an antigen peptide
invariant chain (Ii)
polypeptide that associates with major histocompatibility complex (MHC) class II proteins in the endoplasmic reticulum and prevents them from binding peptides there. Ii is degraded in endosomes, enabling MHC class II molecules to bind endosomal peptides
cross presentation
process that occurs within dendritic cells whereby antigen of extracellular origin is presented by MHC class I molecules