What is co-expressed with a TCR?
Compare and contrast an Ig and a TCR
Ig recognize macromolecules and small enzymes, TCR recognize pieces of antigens (peptides) that are presented to them by MHC on APCs; TCR are more diverse than Ig, but each clone for a unique antigen; antigen recognition is mediated by the variable region of heavy and light chains of membrane IG, in TCR recognition is mediated by the variable region of α and β chains
Name the two classes of TCR. Which is more common?
α:β or γ:δ, α:β make up 90-95% of all TCRs
What is antigen processing?
the process by which peptides are generated from larger polypeptides
What is the difference btwn CD8 and CD4 T cells?
What is a major histocompatibility complex (MHC)?
a cluster of closely linked genes on chromosome 6 that encode proteins that control T cell mediated immune responses, determine the fate of transplanted tissues
What is another name for a MHC in humans?
HLA (human leukocyte antigens)
What are the two types of MHC? How do they differ in structure and function?
class 1 and class 2; MHC 1 present peptides that are intracellular in origin, MHC II present peptides from extraceulllar pathogens both MHCs bind peptides and present them the T cells
CD8 recognize what kind of MHC?
CD4 recognize what kind of MHC?
What enables peptides to bind to MHC molecules?
What does the TCR recognize and bind to?
The anchor residue and the MHC molecule
How do HLA molecules differ?
the cell type they are expressed on; the peptide displayed; peptide generation pathways; the type of T cell they talk to
Name 3 common MHC I isotypes
HLA-A, HLA-B and HLA-C; they are each highly polymorphic
Name 3 common MHC class II isotypes
HLA-DP (polymorphic); HLA DQ (polymorphic); HLA-DR( highly polymorphic/oligomorphic)
Where are MHC 2 found?
On APCs and thymic epithelium
Where are MHC 1 found?
on the body's of nucleated cells (except RBCs)
Name 3 cells that are APCs
B cells, macrophages and dendritic cells
How are MHC genes inherited and expressed?
they are inherited as haplotypes and are co-dominant; heterozygous haplotypes are protective
Describe the steps that lead up to a CD 8 T cell recognizing a pathogen on an MHC 1
1) virus infects cell, 2) viral proteins synthesized in cytoplasm; 3) peptide fragments of viral proteins are bound by MHC I in the ER; the bound peptide is transported by MHC I to the cell surface where they are recognized by CD8 cells
Where does TCR rearrangement occur?
What is a double negative T cell progenitor?
it has not selected to be CD4 or CD8 yet
What is positive selection; where does it occur?
in the cortex of the thymus, immature DN TCR rearranges to become a DP T cells; they are tested for antigen recognition on cortical epithelial cells; the ones that have weak recognition for foreign MHC I and II molecules are allowed to migrate to the medulla and then into general circulation
What is negative selection where does it occur?
Those immature T cells that have too strong of a response or no response to MHC 1 or II receptors on dendritic cells are signaled to initiate apoptosis; occurs in the cortex of the thymus
List the steps in T cells maturation
stem cell→DN Pro-T cell→pre T-cell→ DP immature T cell->mature self tolerant, self-MHC restricted single positive CD4 or CD8 T cells
Which occurs first? Positive or negative selection in the thymus?
How is CD8 or CD4 status determined?
By chance; if the DP interacts with an MHC I molecule→ CD8; if MHC II→CD4
Draw the structure and understand the functions of T cell receptors
they are dimers, with a variable, constant and transmembrane region; binding sites are either α:β or γ:δ;
What is an alloantigen?
antigens that vary between members of the same species; they come into play with transplant surgery when the graft tissue is rejected by the host because the host recognizes the MHCs on the grafted tissue as "foreign"
What are the functions of gamma-delta+ T cells?
they are found primarily in the epithelial tissue; their function is not well understood but it seems that these cells are not restricted to recognizing peptide antigens associated with MHCs
What do regulatory T cells (Treg's) do?
They regulate the activation of naïve autoreactive CD4 and CD8 cells that have the potential to attack the body's healthy tissue; they help make sure that CD8 and CD4 cells do not accidentally damage healthy tissue during an immune response and that they are decommissioned when the pathogen has been killed