Ch. 3. Antigen Capture and Presentation to Lymphocytes. Flashcards
MHC restriction
The characteristic of T lymphocytes that they recognize a foreign peptide antigen only when it is bound to a particular allelic form of an MHC molecule.
Antigen-presenting cell (APC)
A cell that displays peptide fragments of protein antigens, in association with MHC molecules on its surface and activates antigen-specific T cells.
In addition to displaying peptide-MHC complexes, APCs also express costimulatory molecules to optimally activate T lymphocytes.
Dendritic cells
Bone marrow-derived cells found in epithelial and lymphoid tissues that are morphologically characterized by thin membranous projections. Many subsets of dendritic cells exist with diverse functions.
Classical (conventional) dendritic cells function as innate sentinel cells and APCs for naive T lymphocytes, and they are important for initiation of adaptive immune responses to protein antigen.
Immature (resting) classical dendritic cells are important for induction of tolerance to self antigens.
Plasmacytoid dendritic cells (pDCs) produce type I interferons in response to viruses.
Human leukocyte antigens (HLAs)
MHC molecules expressed on the surface of human cells. Human MHC molecules were first identified as alloantigens on the surface of white blood cells (leukocytes) that bound serum antibodies from individuals previously exposed to other individuals’ cells (e.g., mothers or transfusion recipients).
Class I major histocompatibility complex (MHC) molecule
One of two forms of polymorphic heterodimeric membrane proteins that bind and display peptide fragments of protein antigens on the surface of APCs for recognition by T lymphocytes.
All nucleated cells express class I MHC surface proteins.
Class I MHC molecules usually display peptides derived from proteins that are proteolytically processed by proteasomes in the cytosol of the cell, for recognition by CD8+ T cells.
Class II major histocompatibility complex (MHC) molecule
One of two forms of polymorphic heterodimeric membrane proteins that bind and display peptide fragments of protein antigens on the surface of APCs for recognition by T lymphocytes.
Class II MHC molecules usually display peptides derived from extracellular proteins that are internalized into phagocytic or endocytic vesicles, for recognition by CD4+ cells.
MHC haplotype
The set of MHC genes present on each chromosome.
Antigen processing
The intracellular conversion of protein antigens derived from the extracellular space or the cytosol into peptides and loading of these peptides onto MHC molecules for display to T lymphocytes.
Proteasome
A large multiprotein enzyme complex with a broad range of proteolytic activity that is found in the cytoplasm of most cells and generates from cytosolic proteins the peptides that bind to class I MHC molecules.
Proteins are targeted for proteasomal degradation by covalent linkage of ubiquitin molecules.
Transporter associated with antigen presentation (TAP)
An ATP-dependent peptide transporter that mediates the active transport of peptides from the cytosol to the site of assembly of class I MHC molecules inside the endoplasmic reticulum.
TAP is a heterodimeric molecule composed of TAP-1 and TAP-2 polypeptides, both encoded by genes in the MHC.
Because antigenic peptides are required for stable assembly of class I MHC molecules, TAP-deficient animals express few cell surface class I MHC molecules, which results in diminished development and activation of CD8+ T cells.
Invariant chain (I_i)
A nonpolymorphic protein that binds to newly synthesized class II MHC molecules in the endoplasmic reticulum.
The invariant chain prevents loading of the class II MHC-peptide-binding cleft with peptides present in the endoplasmic reticulum, so such peptides are left to associate with class I molecules.
The invariant chain also promotes folding and assembly of class II molecules and directs newly formed class II molecules to the endosomal compartment where peptide loading takes place.
Cross-presentation (cross-priming)
A mechanism by which a dendritic cell activates (or primes) a naive CD8+ CTL specific for the antigens of a third cell (e.g., a virus-infected or tumor cell).
Cross-presentation occurs, for example, when protein antigens from an infected cell are ingested by a dendritic cell and the microbial antigens are processed and presented in association with class I MHC molecules, unlike the general rule for phagocytosed antigens, which are presented in association with class II MHC molecules.
The dendritic cell also provides costimulation for the T cells.
Also called cross-priming.
Immunodominant epitope
The epitope of a protein antigen that elicits most of the response in an individual immunized with the native protein.
Immunodominant epitopes correspond to the peptides of the protein that are proteolytically generated within APCs, bind most avidly to MHC molecules, and are most likely to stimulate T cells.
Follicular dendritic cells (FDCs)
Cells in lymphoid follicles of secondary lymphoid organs that express complement receptors and Fc receptors, and have long cytoplasmic processes that form a meshwork integral to the architecture of the follicles.
Follicular dendritic cells display antigens on their surface for B cell recognition and are involved in the activation and selection of B cells expressing high-affinity membrane Ig during the process of affinity maturation.
They are non-hematopoietic cells (not of bone marrow origin).
Class II-associated invariant chain peptide (CLIP)
A peptide remnant of the invariant chain that sits in the class II MHC peptide-binding cleft and is removed by action of the HLA-DM molecule before the cleft becomes accessible to peptides produced from extracellular protein antigens that are internalized into vesicles.
