Podcast
Questions and Answers
What do MHC genes code for?
What do MHC genes code for?
The expression of cell surface proteins that function, among other things, to present antigen.
Where are MHC genes found in humans?
Where are MHC genes found in humans?
Chromosome 6.
What is the term for MHC in humans?
What is the term for MHC in humans?
HLA.
What is the term for MHC in mice?
What is the term for MHC in mice?
What are MHC proteins often called?
What are MHC proteins often called?
How does a recipient's immune system recognize MHC molecules in a tissue transplant?
How does a recipient's immune system recognize MHC molecules in a tissue transplant?
Where are MHC class I molecules found?
Where are MHC class I molecules found?
Where are MHC class I genes found?
Where are MHC class I genes found?
What is the primary immunological function of MHC class I?
What is the primary immunological function of MHC class I?
Where are MHC class II molecules normally found?
Where are MHC class II molecules normally found?
What is the primary immunological function of MHC class II?
What is the primary immunological function of MHC class II?
What do MHC class III genes code for?
What do MHC class III genes code for?
Which MHC class I genes code for an alpha chain?
Which MHC class I genes code for an alpha chain?
In MHC class I, where are the 3 globular domains located?
In MHC class I, where are the 3 globular domains located?
What is B2 microglobulin?
What is B2 microglobulin?
Where does B2 microglobulin come from?
Where does B2 microglobulin come from?
What do the a1 and a2 chains form in MHC class I?
What do the a1 and a2 chains form in MHC class I?
What occurs in the a1 and a2 domains of MHC class I?
What occurs in the a1 and a2 domains of MHC class I?
What are MHC class II molecules composed of?
What are MHC class II molecules composed of?
In MHC class II molecules, what is between the a and b chain?
In MHC class II molecules, what is between the a and b chain?
What prevents self-antigens from binding to MHC class II?
What prevents self-antigens from binding to MHC class II?
How many distinct MHC class I molecules will any nucleated cell express?
How many distinct MHC class I molecules will any nucleated cell express?
How many different MHC class II molecules will APC cells express at least?
How many different MHC class II molecules will APC cells express at least?
What is determinant selection model?
What is determinant selection model?
What are endogenous antigens?
What are endogenous antigens?
What are proteosomes?
What are proteosomes?
Processed endogenous peptides are transported to the _________ where they are loaded into the ___________ of newly synthesized MHC class I molecules.
Processed endogenous peptides are transported to the _________ where they are loaded into the ___________ of newly synthesized MHC class I molecules.
What do MHC genes code for?
What do MHC genes code for?
Where are MHC genes found in humans?
Where are MHC genes found in humans?
What is the MHC termed in humans?
What is the MHC termed in humans?
What is the MHC termed in mice?
What is the MHC termed in mice?
What are MHC proteins often called?
What are MHC proteins often called?
How does a recipient's immune system recognize MHC molecules in a tissue transplant?
How does a recipient's immune system recognize MHC molecules in a tissue transplant?
Where are MHC class I molecules found?
Where are MHC class I molecules found?
Where are MHC class I genes found?
Where are MHC class I genes found?
What is the primary immunological function of MHC class I?
What is the primary immunological function of MHC class I?
What are MHC class II genes a product of?
What are MHC class II genes a product of?
Where are MHC class II molecules found?
Where are MHC class II molecules found?
What is the primary immunological function of MHC class II?
What is the primary immunological function of MHC class II?
What does MHC class III contain genes that code for?
What does MHC class III contain genes that code for?
Which MHC class I genes code for an alpha chain?
Which MHC class I genes code for an alpha chain?
In MHC class I, where are the three globular domains located?
In MHC class I, where are the three globular domains located?
Describe B2 microglobulin.
Describe B2 microglobulin.
B2 microglobulin is not produced by which chromosome?
B2 microglobulin is not produced by which chromosome?
In MHC class I, what do the a1 and a2 chains form?
In MHC class I, what do the a1 and a2 chains form?
What occurs in the a1 and a2 domains of MHC class I?
What occurs in the a1 and a2 domains of MHC class I?
MHC class II molecules are composed of which chains?
MHC class II molecules are composed of which chains?
MHC class II, both a and b chains have what?
MHC class II, both a and b chains have what?
What is between the a and b chains in MHC class II molecules?
What is between the a and b chains in MHC class II molecules?
What accounts for binding specificity in MHC class II molecules?
What accounts for binding specificity in MHC class II molecules?
What prevents self-antigens from binding in MHC class II molecules?
What prevents self-antigens from binding in MHC class II molecules?
How many distinct MHC class I molecules will any nucleated cell express?
How many distinct MHC class I molecules will any nucleated cell express?
MHC class II APC cells will express at least how many different molecules?
MHC class II APC cells will express at least how many different molecules?
Expression of MHC molecules is what?
Expression of MHC molecules is what?
Each MHC molecule must be able to do what?
Each MHC molecule must be able to do what?
What is the determinant selection model?
What is the determinant selection model?
What are immunodominant epitopes?
What are immunodominant epitopes?
What types of antigens do MHC class I present?
What types of antigens do MHC class I present?
What are endogenous antigens?
What are endogenous antigens?
What are proteasomes?
What are proteasomes?
Processed endogenous peptides are transported to the __________.
Processed endogenous peptides are transported to the __________.
Antigen-loaded MHC class I molecules are then transported through the __________.
Antigen-loaded MHC class I molecules are then transported through the __________.
MHC class I molecules that are not loaded with antigen are __________.
MHC class I molecules that are not loaded with antigen are __________.
MHC class II molecules present antigens of what origin?
MHC class II molecules present antigens of what origin?
MHC class II are synthesized in the _______ and transported through the ________.
MHC class II are synthesized in the _______ and transported through the ________.
MHC class II gamma chain is hydrolyzed off the __________.
MHC class II gamma chain is hydrolyzed off the __________.
Once the antigen-loaded MHC molecule is expressed on the cell surface, what can it do?
Once the antigen-loaded MHC molecule is expressed on the cell surface, what can it do?
What do CD4, CD8, and TCR recognize in the immune system?
What do CD4, CD8, and TCR recognize in the immune system?
The CDR 1 and 2 regions bind to what component of MHC?
The CDR 1 and 2 regions bind to what component of MHC?
While MHC molecules display specificity, what do they have broader specificity than?
While MHC molecules display specificity, what do they have broader specificity than?
Class I molecules bind peptides that are _ to _ amino acids long.
Class I molecules bind peptides that are _ to _ amino acids long.
Class II molecules bind __ to __ amino acid length peptides, although the optimal length is __ to __ amino acids.
Class II molecules bind __ to __ amino acid length peptides, although the optimal length is __ to __ amino acids.
What do MHC molecules bind?
What do MHC molecules bind?
How do T cells discriminate between self and non-self?
How do T cells discriminate between self and non-self?
What type of structures are T cell epitopes often?
What type of structures are T cell epitopes often?
Many T cell epitopes are processed peptide fragments from where?
Many T cell epitopes are processed peptide fragments from where?
Study Notes
Major Histocompatibility Complex (MHC) Overview
- MHC genes encode proteins that present antigens on cell surfaces, aiding in immune responses.
- Human MHC is identified as HLA, while in mice it is referred to as H-2.
- MHC genes in humans are located on chromosome 6; in mice, they reside on chromosome 17.
MHC Class I
- MHC class I molecules are present on all nucleated cells and are essential for presenting endogenous antigens to CD8+ T cells (cytotoxic T lymphocytes).
- Key regions for MHC class I genes include HLA-A, HLA-B, and HLA-C, which code for an alpha chain involved in the formation of a binding groove for antigens.
- B2 microglobulin, a non-covalently linked small globular peptide, comes from chromosome 15 and is associated with MHC class I.
- MHC class I presents peptides that are typically 8-11 amino acids in length, with structural diversity in the a helices and b pleated sheets enhancing binding specificity.
MHC Class II
- MHC class II is primarily found on professional antigen-presenting cells (APCs), such as B cells and dendritic cells, and presents exogenous antigens to CD4+ T helper cells.
- Composed of both an alpha (containing a1 and a2 domains) and a beta (containing b1 and b2 domains) chain, MHC class II molecules have a transmembrane domain and a cytoplasmic tail on both chains.
- The antigen-binding groove in MHC class II is formed between the two chains, enabling the binding of larger peptides (10-30 amino acids, optimal being 12-16).
- MHC class II molecules prevent self-antigen binding initially by associating an invariant chain that occupies the antigen-binding site during intracellular assembly.
Peptide Binding and Presentation
- MHC molecules exhibit broad specificity, allowing them to bind both foreign and self-peptides, crucial for T cell recognition.
- T cell receptors (TCRs) recognize the peptide-MHC complex, with CDR regions binding specifically to MHC helices and the processed antigen.
- Determinant selection model describes the selective binding of peptides to MHCs, influencing which peptides are presented and eliciting immune responses.
- Immunodominant epitopes are those that primarily stimulate an immune reaction, which often consist of hydrophobic or aromatic peptide fragments.
Expression and Genetic Diversity
- Each nucleated cell expresses six distinct MHC class I molecules due to inheritance from both parents.
- MHC class II molecules, formed from two chains with three major genes (DR, DP, DQ) for each chain, can display varying configurations, increasing possible antigen presentation.
- MHC expression is inherently limited, ensuring that a variety of peptides can compete for binding and presentation. However, not every peptide processed within the cell is presented outside.
Importance in Immune Response
- MHC molecules play a critical role in the immune system, enabling T cells to differentiate between self and non-self entities through their unique TCR specificity.
- Antigen-loaded MHC molecules that reach the cell surface can present antigens to any T cell with appropriate receptors, which is vital for mounting an effective immune response.
- Class I molecules are crucial for recognizing and responding to endogenous threats, typically viral, while class II molecules are key for recognizing exogenous antigens encountered by APCs.
Key Mechanisms and Processes
- Proteasomes degrade intracellular proteins into peptide fragments that are 8-11 amino acids long, suitable for MHC class I.
- Processed peptides are transported to the rough endoplasmic reticulum to be loaded into MHC class I antigen-binding grooves before being expressed on the cell surface.
- MHC class II molecules, synthesized in the endoplasmic reticulum, fuse within vesicles containing processed antigens from phagocytosis, facilitating external presentation.
Overall, the MHC is vital in shaping the adaptive immune response by presenting diverse peptide antigens, ensuring recognition and response to infections while maintaining self-tolerance.
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Test your knowledge on the Major Histocompatibility Complex (MHC) with these flashcards. Learn about the genes, their functions, and differences between humans and mice. Perfect for students studying immunology or genetics.
