Lecture 6: MHC Binding Flashcards
What is required for a naive T cell to be activated?
- recognize the Ag at the TCR
2. binding of co-stimulatory and co-receptors
What process occurs once a T cell is activated?
- undergoes clonal expansion
What does Th1 cells do?
- release IFN-gamma to activate tissue macrophages
- -rid intracellular microbes - develop cytotoxic T cells
What do Th2 cells do?
1.help B cells proliferate into memory and plasma cells
What is secreted by Th2 to help B cell proliferation?
- IL-4
What does IL-4 do?
- secreted from Th2 cells to help B cell proliferate into memory and plasma cells
What is the TCR, found at the membrane, made of?
- alpha chain and beta chains
2. both form constant and variable regions
What is the Ag-binding site formed of?
- the constant and variable regions of the alpha, beta chains
Can T cells express gamma and delta chains on the TCR?
yes, poor understanding
What is known about the specificity of the gamma, and delta chain TCRs?
- broad specificity
2. bind to HSP and phospholipid Ag
What is the molecular weight of alpha chains in TCR?
- 50kDa
What is the molecular weight of beta chains in TCR?
- 39kDa
What is the location of the constant and variable regions on the TCR?
- constant region, located near the PM so it will always bind to the T cell
- variable regions is presented to the Ag binding site to provide different attachments for different Ag
What is CD3 and why is it significant to TCR?
- signaling complex of gamma, delta, espilon chains
- acts to help with APC presentation/binding to MHC
- therefore is a co-receptor to activate T cells
Th cells are restricted to recognizing peptides presented on what MHC class?
MHC II on the APC
Tc cells are restricted to killing cells presented on what MHC class?
MHC I
What type of Ag is able to bind peptides and is critical for Ag presentation?
human leukocyte Ag (HLA)
What are human leukocyte Ag (HLA)?
polymorphic genes that are the human equivalent of MHC class I and class II
Which class of HLA is expressed on all nucleated cells?
MHC class I
HLA-A, HLA-B, HLA-C are all ___________
MHC class I genes that encode a polymorphic heavy chain
What do the polymorphic heavy chains of class I HLA genes combine with?
Beta2-microglobulin
What is the code for MHC class II human leukocyte antigen (HLA)?
-DP, -DR, -DQ
Do MHC class II HLA genes contribute to peptide-binding groove?
yes, with use of alpha and beta chains
How long is the amino acid sequence that MHC class I regions can bind? And MHC II?
- 8 to 10
2. 10 to 20
In MHC class I, the peptide binding cleft is formed by______?
the polymorphic alpha chain, which also provides attachment to the PM
In MHC class II, the peptide binding cleft is formed by __________?
both the alpha 1 and beta 1 complex units
Which cells express MHC class I?
all nucleated cell
Which cells express MHC II?
- DC
- Mononuclear phagocytes
- B lymph
- endothelium cells
- thymic epithelium
Peptide antigens that bind with MHC I molecules come from where and use what process to make it to this point?
- come from viruses that infect host cells
2. use endogenous pathway
If a peptide Ag were to bind with MHC II, where is this Ag taken up from and what TCR interacts with it?
- taken up from environment via exogenous pathway
2. interacts with CD4+ T cells
What effect will a Dendritic cell have on a Naive T cell if an Ag is presented?
The naive T cell will be activated, undergo clonal expansion, and differentiate into effector T cells
Effector T cell binds with a macrophage, what is the end result?
The macrophage is activated and thus begins cell mediated immunity
What happens if a B cell, with antigen, interacts with an effector T cell?
Causes B cell activation that produces antibodies, and therefore a humoral response.
What ports of entry allows a microbial Ag to be transported to the regional lymph nodes?
- entrance via the skin
- the GI
- Respiratory tract
- -DC capture and transport them to regional LN
What port of entry causes microbial Ag to be transported to the spleen?
Ag that enter the bloodstream
Ag that enter the blood stream, and encounter APC, are transported where>
the spleen
Ag the enter via the skin, GI, or respiratory tracts, or other mucosal tracts except the eye are transported where?
To regional lymph nodes
What is IFN-gamma able to produce?
stimulates the MHC II expression and increases activation of CD4+ cells
What compounds are able to activate MHC I, and therefore activation of CD8+ T cells?
IFN-gamma and Type I interferons
What is HLA-DM?
provides the most relevant Ag for the APC to present
What are the 3 functions of HLA-DM?
- dissociates CLIP from the peptide binding groove of MHC II
- Stabilizes and prevents degradation of empty MHC II
- Helps binding of Ag fragments to the binding groove
Draw out the pathways for MHC I and MHC II uptake and processing of microbe
yes
Are DC able to present Ag via MHC I pathways?
yes this is cross presentation
What is the process of cross presentation?
- infected host cell is taken up by DC
- The viral Ag enters the DC cytosol
- MHC I are bound with the viral Ag peptide
- this is presented to CD8 cells with a costimulator
- T cells generate effector response
What is an immunodominant peptide?
Any of the peptides having a strong affinity for binding with class I or II histocompatibility antigens and for stimulating a response by T lymphocytes.
How are immunodominant peptides produced and what are the benefits of them?
Immunodominant peptides are produced by antigen processing, are expressed on the surface of macrophages and other antigen-presenting cells, and may be useful both in desensitizing people to allergens and in vaccine production.
