Exam 3: Chapter 5 Flashcards
What are naïve CD8+ T cells?
Cells activated by MHC Class 1 peptides presented by APCs
What are the different forms of any given gene called?
Alleles
What is antigen processing?
Process in which pathogens and other proteins are chopped up into smaller pieces called peptides
How are the MHC genes arranged on the chromosome?
The class 1 and class 2 gene families are in separate regions and are separated by the class 3 region
How do the CDR regions of the TCR contact the peptide MHC?
CDRs 1 and 2 bind to the alpha helices of the MHC, and CDR 3 binds the peptide
How many T cell receptors (TCRs) are expressed by each T cell?
1
What do chaperone proteins do, in terms of MHC Class 1?
Aid in the assembly of the MHC Class 1 heterodimer and facilitate the binding of peptides
What is directional selection?
The type of selection that favors one allele over others due to its ability to protect against a pathogen
What are the unique features of helper T cells?
They are CD4+ and help activate effector cells to fight extracellular pathogens
What are the specifics of the MHC Class 1 binding pocket?
Binds to the ends of peptides, prefers peptides of ~ 9 AAs
In which MHC type does allotype equal isoform?
MHC Class 1
What do HLA-E and HLA-G do?
Present peptides to NK cells only
Which class region also includes genes involved in the immune response?
Class 2
What components form the CD3 complex?
2 epsilon domains, 2 zeta domains, 1 delta domain, and 1 gamma domain
What kind of combinatorial diversity is observed in the TCR alpha chain?
VJ combination (like the light chain of antibodies)
What is MHC called in humans?
Human Leukocyte Antigen Complex (HLA)
How are the binding sites of TCRs determined?
By the hypervariable regions, or CDRs
Which MHC class has multiple possible genes for each isotype?
Class 2
Compare and contrast the structure of an antibody versus a T cell receptor.
Both TCRs and antibodies are made up of variable and constant regions. Antibodies are formed from 4 proteins, while TCRs are formed from 2 proteins. Antibodies can be on the cell surface or secreted, while TCRs are only ever present on cell surfaces
What are the unique features of cytotoxic T cells?
They are CD8+, are activated by intracellular pathogens, and kill infected cells
What is degenerate specificity?
The ends of the peptide and specific anchor residues are recognized rather than individual peptides, allowing MHCs to bind to a wider variety of peptides
What is the function of the proteosome?
To chop proteins into peptides
How are the peptides generated by the proteosome transported into the ER?
By the Transporter associated with Antigen Processing (TAP)
What syndrome is associated with TAP mutations?
Bare-Lymphocyte Syndrome - less than 1% of the normal amount of Class 1 MHC is present on the cell surface
What do HLA-DP, HLA-DQ, and HLA-DR do?
Present peptides to CD4+ T cells
What are alloantibodies?
Antibodies produced by a pregnant woman in response to the paternal MHC present within the fetus’s cells
What is gene conversion?
When one gene unequally shares genetic information with another gene
What do HLA-DM and HLA-DO do?
Regulate peptide loading in the phagolysosome
What are the two mechanisms that generate diversity in MHC molecules?
- MHC gene families contain multiple chain genes
2. Genetic polymorphisms
What happens once the MHC Class 2 molecule reaches the vesicle?
The invariant chain is cleaved, leaving behind the CLIP fragment that still prevents peptide binding
What do T cell receptors recognize?
Peptide antigens that are presented by MHC
When TCR binds, what does it make contact with?
Both the peptide and the MHC molecule
What is cross presentation?
When MHC Class 1 molecules present extracellular antigens
Where do the hypervariable regions of TCRs occur?
In the loops between the Ig domains
What are the two types of diversity that contribute to differences in the TCR alpha and beta chains?
Combinatorial diversity and junctional diversity
Which MHC class do CD4+ T cells interact with?
MHC Class 2
What is the role of the invariant chain?
To block the binding of peptides to the MHC Class 2 molecule while it is still in the ER and to deliver the Class 2 molecule to the appropriate vesicles for peptide binding
How is CLIP removed so that MHC Class 2 molecules can bind peptides?
Via the action of HLA-DM
What are gamma-delta T cells?
T cells that express a gamma:delta heterodimer
What is the immunoproteosome?
A special form of the proteosome for MHC Class 1, which is induced by Ifn-gamma
What are the two types of MHC?
MHC Class 1 and MHC Class 2
What is interallelic conversion?
When two alleles of the same gene exchange genetic information equally
What are the different HLA Class 1 isotypes?
HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G
What is the combination of allotypes that forms an MHC molecule called?
Isoform
Why is it important that MHC molecules are polymorphic?
Being polymorphic provides MHC molecules with degenerate binding specificity, which allows them to bind a wide variety of peptides
What are alloreactive T cells?
T cells that will recognize self-peptides presented by allogenic MHC
What is antigen presentation?
When MHC displays a peptide on the cell surface
What are the specifics of the MHC Class 2 binding pocket?
Binds with the side chains of peptides, and thus can bind to larger peptides than MHC Class 1
What are the different HLA Class 2 isotypes?
HLA-DM, HLA-DO, HLA-DP, HLA-DQ, HLA-DR
What is MHC restriction?
The requirement that T cells must recognize both the peptide and the specific MHC structure in order to be activated
What is balancing selection?
The type of selection that acts to maintain MHC diversity by selecting for heterozygotes with haplotypes that minimally overlap
What is an alloreaction?
When a transplanted organ presents self-peptides complexed with allogenic MHC, leading to rejection
What do alloantibodies do?
Attack transplanted tissues in a woman if they have the same MHC as a man who fathered a previous pregnancy
What is ERAP?
A peptidase that shortens peptides so that they fit into the MHC Class 1 molecule
What part of MHC Class 2 does CD4 bind to?
The beta-2 domain
What is directional selection caused by?
An epidemic disease
What are alpha-beta T cells?
T cells that express an alpha:beta heterodimer
What is the function of cytotoxic T cells?
To kill infected cells
How does TCR interact with antigen?
Via cell-to-cell interactions
What is the role of calnexin?
To stabilize the Class 1 heavy chain until Beta-2 microglobulin binds
What forms the antigen binding domain of the TCR?
The variable regions of the TCR alpha and TCR beta chains
What is the MHC Class 1 molecule composed of?
An MHC heavy chain (with domains alpha-1, alpha-2, alpha-3, and a transmembrane domain) and Beta-2 microglobulin
What molecules form the peptide-loading complex?
Class 1 heterodimer, calreticulin, tapasin, TAP, ERp57, and PDI
Where do Class 2 peptides bind?
In vesicles known as the MHC Class 2 compartment
What part of MHC Class 1 does CD8 bind to?
The alpha-3 domain
What do HLA-A, HLA-B, and HLA-C do?
Present peptides to CD8+ T cells and NK cells
How can APCs be activated, if not infected by the virus itself?
By phagocytosing infected dead cells
Why is it important that the cell is compartmentalized?
Peptides derived from intracellular pathogens (MHC Class 1) and are generated in a separate compartment than peptides derived from extracellular pathogens (MHC Class 2)
Which Class 1 HLA remains intracellular with an unknown function?
HLA-F
What kind of combinatorial diversity is observed in the TCR beta chain?
VDJ combination (like the heavy chain of antibodies)
What is a unique feature of gamma-delta T cells?
They can bind antigens that are not presented by MHC
What are the proteins encoded for by different alleles called?
Allotypes
What is SCID?
Severe Combine Immunodeficiency - null mutations in RAG 1 and RAG 2 block TCR and immunoglobulin rearrangements, leading to a lack of B and T cells
What is the MHC Class 2 molecule composed of?
An alpha chain and a beta chain, each containing a transmembrane domain, an Ig-like domain, and a peptide bonding domain
What is the combination of MHC alleles on the chromosome called?
Haplotype
How are new MHC genes generated?
Point mutations and recombination
What is the CD3 complex?
Complex required for the proper transport of TCR that also relays signals into the cell once TCR binds its antigen
Which MHC class do CD8+ T cells interact with?
MHC Class 1
Why can allogenic MHC alloreactions be treated, but alloantibody alloreactions cannot?
There are drugs available that can inhibit T cell activation, but none that can inhibit the antibody response
What is the function of helper T cells?
To help activate other effector cells
What regions of a peptide do MHC molecules recognize?
The ends and the backbone
Why are alpha-beta T cells and gamma-delta T cells mutually exclusive?
The delta chain locus is contained within the alpha chain locus, and gets deleted when the alpha chain is rearranged
How are autologous MHC isoforms and allogenic MHC isoforms different?
The self MHC isoforms are referred to as autologous, while all others are considered allogenic
