Chapter 5- Antigen Recognition by T cells Flashcards
T lymphocytes (T cells)
Cells that recognize conserved epitopes (antigens) in the context of MHC molecules. They have different roles in adaptive immunity
T-cell receptor (TCR)
Highly variable receptor expressed by T lymphocytes. It is a membrane bound heterodimer that is not secreted, unlike antibodies. They have a similar structure to immunoglobulins, are produced by somatic recombination, and have highly diverse antigen specificities. Similar to B cells, a clone of T cells expresses just one form of antigen receptor, but each clone has a different specificity for antigen
Naive cell
A cell that is circulating in the body and has not seen antigen. Naive T cells have left the thymus for the circulation
Major histocompatibility complex (MHC) molecule
T cells recognize antigens as a composite structure on the human cell surface that consists of the pathogen-derived peptide antigen and a bound MHC molecule, which is a glycoprotein. The combination of the peptide and the MHC molecule acts as a ligand for the T cell receptor
Polymorphism
The existence of different variants of a gene or trait in a population. MHC genes have a high polymorphism. Differences between the MHC molecules of an organ donor and recipient are the main reason for organ rejection.
Antigenic drift
Antigens change over time. Influenza is one example- small mutations are introduced through the viral replication process and its “coat” is changed. These antigens are targeted by vaccines, which is why the vaccine must be changed each year to target the new antigens
Listeria monocytogenes
Pathogenic agent of listeriosis, a disease linked to deli meats and cheeses. There are 1,600 cases per year and 260 deaths. Impacts pregnant women, newborns, the elderly, &
immunocompromised individuals. L. monocytogenes gains access to cells and can escape the macrophages. Also uses actin to “shoot” itself from one cell to the next. Demonstrates what happens when microbes are “hidden” from antibodies when they live inside cells. Antibodies cannot penetrate the cells
Antigenic shift
When enough mutations occur in a virus to create an entirely new virus
Importance of T cells and antigen presentation
Genetic differences in organ transplants or skin grafts are identified as “non-self” antigens, which can lead to rejection.
T cell receptor (TCR) structure
Contains single alpha (α) and beta (β) chains. Has a variable (V) region and constant (C) region, and a short cytoplasmic tail that acts as a membrane-anchoring domain. The structure represents a membrane-bound Fab fragment. It has only one antigen binding site, located at the ends of the chains. Receptors are always membrane bound, not secreted like an antibody. Unlike in B cells, there is no process of somatic hypermutation after the T cell is stimulated with an antigen, and there is no isotype switching
T-cell receptor gene organization
The genes encoding α and β chains have a germline organization, like that of immunoglobulin genes. They are also composed of arrays of gene arrangements that need to be rearranged to form a functional gene- V, D, and J, as found in immunoglobulins
TCR-alpha gene locus
TCR-alpha gene locus is on chromosome 14: has V-alpha and J-alpha gene segments
TCR-beta gene locus
TCR-beta gene locus is on chromosome 7: V-beta, D-beta, and J-beta gene segments
T-cell receptor diversity
Generated by gene rearrangement. This gene organization and process is homologous to that of immunoglobulin gene segments. One C-alpha gene and two C-beta genes; not directly
related to effector function like with antibodies. TCR gene segments are flanked by 12-bp and 23-bp RSSs. The same enzymes are involved (RAG1/RAG2, DNA-PK,
Artemis, etc.). Va-Ja recombination for TCR-alpha DB-JB, VB to DJB recombination for TCRB
Where does TCR recombination occur?
In the thymus
