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Questions and Answers
What increases the expression of MHC class II on macrophages and dendritic cells?
What increases the expression of MHC class II on macrophages and dendritic cells?
Which of the following is true about MHC I and II?
Which of the following is true about MHC I and II?
What happens if a foreign antigenic peptide does not fit the MHC molecule?
What happens if a foreign antigenic peptide does not fit the MHC molecule?
Why are heterozygous animals more likely to respond to a variety of antigens?
Why are heterozygous animals more likely to respond to a variety of antigens?
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Which animal species is at risk for decimation by infectious pathogens due to genetic homogeneity?
Which animal species is at risk for decimation by infectious pathogens due to genetic homogeneity?
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What is the function of MHC class I molecules in presenting antigens?
What is the function of MHC class I molecules in presenting antigens?
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What is the main discovery recognized by the Snell Prize?
What is the main discovery recognized by the Snell Prize?
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What is the term used to describe the region that controls graft rejection or survival?
What is the term used to describe the region that controls graft rejection or survival?
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What is a typical feature of Class I MHC molecules?
What is a typical feature of Class I MHC molecules?
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Which of the following species has the most functional Class I loci?
Which of the following species has the most functional Class I loci?
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Which of the following statements is true about histocompatibility molecules?
Which of the following statements is true about histocompatibility molecules?
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Which class of MHC gene loci is less polymorphic and located outside the MHC on a different chromosome?
Which class of MHC gene loci is less polymorphic and located outside the MHC on a different chromosome?
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What is the main function of T cells?
What is the main function of T cells?
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Which type of cells are involved in the activation of T cells?
Which type of cells are involved in the activation of T cells?
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What is the role of MHC molecules in T cell activation?
What is the role of MHC molecules in T cell activation?
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How were MHC genes initially discovered?
How were MHC genes initially discovered?
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Which of the following is a possible outcome of a skin graft between two animals?
Which of the following is a possible outcome of a skin graft between two animals?
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Which of the following is a common characteristic of MHC molecules?
Which of the following is a common characteristic of MHC molecules?
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Which method is used to determine polymorphism in both class I and class II regions in cattle?
Which method is used to determine polymorphism in both class I and class II regions in cattle?
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What is a possible explanation for why a particular MHC allele makes an animal more susceptible to a certain disease?
What is a possible explanation for why a particular MHC allele makes an animal more susceptible to a certain disease?
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Which of the following is a consequence of an overreaction or cross-reaction of the immune system?
Which of the following is a consequence of an overreaction or cross-reaction of the immune system?
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What is the significance of MHC typing in cattle?
What is the significance of MHC typing in cattle?
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Which of the following diseases is associated with MHC alleles in goats?
Which of the following diseases is associated with MHC alleles in goats?
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What is the role of MHC proteins in the immune response?
What is the role of MHC proteins in the immune response?
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Which of the following is a characteristic of MHC class I molecules?
Which of the following is a characteristic of MHC class I molecules?
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Which of the following is a function of the class III genes in the MHC?
Which of the following is a function of the class III genes in the MHC?
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Which of the following is the correct gene structure for MHC molecules?
Which of the following is the correct gene structure for MHC molecules?
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Which of the following is the most variable part of the MHC class I molecule?
Which of the following is the most variable part of the MHC class I molecule?
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Which of the following is a characteristic of T cell receptors (TCR)?
Which of the following is a characteristic of T cell receptors (TCR)?
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Which of the following is a common misconception about self peptides presented by MHC molecules?
Which of the following is a common misconception about self peptides presented by MHC molecules?
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Which of the following is a characteristic of MHC class II molecules?
Which of the following is a characteristic of MHC class II molecules?
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Which of the following is a characteristic of the class III genes in the MHC?
Which of the following is a characteristic of the class III genes in the MHC?
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Which of the following is a characteristic of MHC molecules in individuals?
Which of the following is a characteristic of MHC molecules in individuals?
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What increases the expression of MHC class I molecules?
What increases the expression of MHC class I molecules?
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Which type of cells increase the expression of MHC class II on macrophages and dendritic cells?
Which type of cells increase the expression of MHC class II on macrophages and dendritic cells?
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What is the effect of a foreign antigenic peptide that does not fit the MHC molecule?
What is the effect of a foreign antigenic peptide that does not fit the MHC molecule?
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How does the MHC help in regulating the immune response?
How does the MHC help in regulating the immune response?
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What can be said about heterozygous animals in relation to MHC and immune response?
What can be said about heterozygous animals in relation to MHC and immune response?
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What is the term used to describe the genes responsible for the survival or rejection of a graft?
What is the term used to describe the genes responsible for the survival or rejection of a graft?
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Which animals are at risk of decimation by infectious pathogens due to genetic homogeneity?
Which animals are at risk of decimation by infectious pathogens due to genetic homogeneity?
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How many functional Class I loci do humans typically have?
How many functional Class I loci do humans typically have?
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Which animals may not respond to stimulation with specific antigens based on their MHC haplotypes?
Which animals may not respond to stimulation with specific antigens based on their MHC haplotypes?
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Where are Class Id MHC loci located, which are less polymorphic than Class I loci?
Where are Class Id MHC loci located, which are less polymorphic than Class I loci?
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What is the function of Class I MHC molecules in terms of expression?
What is the function of Class I MHC molecules in terms of expression?
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How many MHC class Ia loci do mice typically have?
How many MHC class Ia loci do mice typically have?
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Why might an animal with MHC alleles unable to bind to a critical antigen succumb to an infection?
Why might an animal with MHC alleles unable to bind to a critical antigen succumb to an infection?
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Which scenario explains how a particular MHC allele can lead to an autoimmune response?
Which scenario explains how a particular MHC allele can lead to an autoimmune response?
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In which case does an animal with specific MHC alleles face a risk of developing progressive arthritis?
In which case does an animal with specific MHC alleles face a risk of developing progressive arthritis?
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How does the binding of an MHC allele to an epitope Z during an infection contribute to disease susceptibility?
How does the binding of an MHC allele to an epitope Z during an infection contribute to disease susceptibility?
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What role do MHC proteins play in disease susceptibility?
What role do MHC proteins play in disease susceptibility?
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How does MHC typing in cattle contribute to understanding disease resistance/susceptibility?
How does MHC typing in cattle contribute to understanding disease resistance/susceptibility?
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What is the main function of T cells in the immune response?
What is the main function of T cells in the immune response?
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Which of the following is not a characteristic of MHC class I molecules?
Which of the following is not a characteristic of MHC class I molecules?
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Which of the following is not a possible outcome of a skin graft between two animals?
Which of the following is not a possible outcome of a skin graft between two animals?
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What was the main discovery recognized by the Snell Prize in 1980?
What was the main discovery recognized by the Snell Prize in 1980?
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Which of the following is not a characteristic of MHC class II molecules?
Which of the following is not a characteristic of MHC class II molecules?
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What happens if a foreign antigenic peptide does not fit the MHC molecule?
What happens if a foreign antigenic peptide does not fit the MHC molecule?
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Which type of cells do not usually express MHC class I molecules?
Which type of cells do not usually express MHC class I molecules?
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What is the common term used to describe the set of MHC alleles present on a chromosome?
What is the common term used to describe the set of MHC alleles present on a chromosome?
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Which MHC class does not participate in antigen presentation?
Which MHC class does not participate in antigen presentation?
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What is the most variable part of the MHC class I molecule?
What is the most variable part of the MHC class I molecule?
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Which type of T lymphocytes recognize peptides presented by MHC class II molecules?
Which type of T lymphocytes recognize peptides presented by MHC class II molecules?
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Which of the following species has the most functional Class I loci?
Which of the following species has the most functional Class I loci?
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Which proteins do Class III loci code for?
Which proteins do Class III loci code for?
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Which type of cells express MHC class II molecules?
Which type of cells express MHC class II molecules?
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Why are heterozygous animals more likely to respond to a variety of antigens?
Why are heterozygous animals more likely to respond to a variety of antigens?
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Which of the following is a common misconception about self peptides presented by MHC molecules?
Which of the following is a common misconception about self peptides presented by MHC molecules?
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Why does the MHC class II gene give greater diversity compared to MHC class I?
Why does the MHC class II gene give greater diversity compared to MHC class I?
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What is the role of MHC class I molecules in antigen presentation?
What is the role of MHC class I molecules in antigen presentation?
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Why is it significant that each individual has 2 complete sets of MHC molecules?
Why is it significant that each individual has 2 complete sets of MHC molecules?
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Why do all individuals not develop autoimmunity even when self peptides are continuously presented?
Why do all individuals not develop autoimmunity even when self peptides are continuously presented?
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Which statement accurately describes the structure of MHC class II molecules?
Which statement accurately describes the structure of MHC class II molecules?
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What is the main reason why each MHC molecule can bind different peptides?
What is the main reason why each MHC molecule can bind different peptides?
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In the context of antigen presentation, what is the significance of T cell receptor (TCR) fine specificity for peptide binding?
In the context of antigen presentation, what is the significance of T cell receptor (TCR) fine specificity for peptide binding?
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What is the main function of MHC class II molecules in the immune response?
What is the main function of MHC class II molecules in the immune response?
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Which type of cells express both MHC class I and class II molecules?
Which type of cells express both MHC class I and class II molecules?
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What is the primary role of T cells in the immune response?
What is the primary role of T cells in the immune response?
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Which type of cells do not usually express MHC class II molecules?
Which type of cells do not usually express MHC class II molecules?
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What is the primary outcome of an incompatible graft between two animals?
What is the primary outcome of an incompatible graft between two animals?
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What is the primary protein responsible for presenting antigens to T cells?
What is the primary protein responsible for presenting antigens to T cells?
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What is the main discovery recognized by the Snell Prize?
What is the main discovery recognized by the Snell Prize?
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Which of the following species has the most functional Class I loci?
Which of the following species has the most functional Class I loci?
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Which of the following is a common misconception about self peptides presented by MHC molecules?
Which of the following is a common misconception about self peptides presented by MHC molecules?
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Which type of cells increase the expression of MHC class II on macrophages and dendritic cells?
Which type of cells increase the expression of MHC class II on macrophages and dendritic cells?
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What is the role of MHC proteins in disease susceptibility?
What is the role of MHC proteins in disease susceptibility?
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Why are heterozygous animals more likely to respond to a variety of antigens?
Why are heterozygous animals more likely to respond to a variety of antigens?
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Which cytokine increases the expression of MHC class II on macrophages and dendritic cells?
Which cytokine increases the expression of MHC class II on macrophages and dendritic cells?
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What is the relationship between the variety of an animal's MHC and its ability to respond to antigens?
What is the relationship between the variety of an animal's MHC and its ability to respond to antigens?
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Which animal species is at risk for decimation by infectious pathogens due to genetic homogeneity?
Which animal species is at risk for decimation by infectious pathogens due to genetic homogeneity?
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Which disease association is true for cattle with the BoLA-DRB3.2*23 allele?
Which disease association is true for cattle with the BoLA-DRB3.2*23 allele?
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Which of the following statements is true about MHC molecules and autoimmune disease?
Which of the following statements is true about MHC molecules and autoimmune disease?
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Which of the following is a common characteristic of MHC molecules?
Which of the following is a common characteristic of MHC molecules?
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Which of the following best describes why a particular MHC allele might make an animal more susceptible to a certain disease?
Which of the following best describes why a particular MHC allele might make an animal more susceptible to a certain disease?
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Which of the following best describes how a certain MHC allele might indirectly contribute to disease progression?
Which of the following best describes how a certain MHC allele might indirectly contribute to disease progression?
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Which of the following methods is used to determine polymorphism in both class I and class II regions in cattle?
Which of the following methods is used to determine polymorphism in both class I and class II regions in cattle?
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Which of the following best describes the role of MHC molecules in the immune response?
Which of the following best describes the role of MHC molecules in the immune response?
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Which of the following best describes the relationship between heterozygous animals and their ability to respond to a variety of antigens?
Which of the following best describes the relationship between heterozygous animals and their ability to respond to a variety of antigens?
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Which of the following best describes the process that occurs when a foreign antigenic peptide does not fit the MHC molecule?
Which of the following best describes the process that occurs when a foreign antigenic peptide does not fit the MHC molecule?
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Study Notes
Regulation of MHC Expression
- Expression of MHC molecules increases in the presence of cytokines during innate and adaptive immune responses.
- IFNα, IFNβ, or IFNγ increase expression of MHC class I.
- IFNγ increases expression of MHC class II on macrophages and dendritic cells.
- Recognition of pathogens by dendritic cells (PAMPs) through Toll-like receptors increases expression of MHC class II.
- Cytokines secreted by CD4+ helper T cells increase expression of MHC class II.
- Macrophages increase expression of MHC class II in the presence of IFNγ secreted by NK cells.
MHC Molecules and Disease
- The MHC regulates the immune response.
- A foreign antigenic peptide that does not fit the MHC molecule will not stimulate an immune response.
- MHC I and II are polymorphic, each allele can bind a set of different antigenic peptides.
- The more variety in an animal's MHC, the more antigens it can respond to.
- Heterozygous animals will express more alleles and bind more antigenic peptides.
- Homozygous animals will have less variety and are more likely not to generate an immune response to certain antigenic peptides.
Examples of MHC and Disease
- African cheetahs are genetically very homogeneous and at risk for decimation by infectious pathogens.
- Infectious peritonitis causes 60% mortality in Cheetahs compared to 1-2% in domestic cats.
- All of the Florida panthers alive in the twentieth century appear to have come from a single female.
- Five Texas pumas were introduced into panther habitat (1995), and the resulting hybrids appear to be doing well.
- The optimal number of MHC genes is a balance between the need to respond to microbial antigens and the need to avoid autoimmune disease.
Disease Associations
- BoLA-Aw7: Resistance to bovine leukemia virus.
- BoLA-Aw12: Susceptibility to bovine leukemia virus.
- BoLA-A*16: Resistance to mastitis.
- BoLA-DRB3.2*23: Increased incidence of severe coliform mastitis.
- BoLA-DRB3*3: Lower risk of retained placenta.
- BoLA-DRB3*22: Lower risk of cystic ovarian disease.
- BoLA-DR locus: Resistance to Dermatophilus.
- ELA-Aw7: Allergic reactions to Culicoides midges.
- ELA-A3, A15, Dw13: Development of sarcoid tumors.
- ELA-A9: Equine recurrent uveitis.
- SLA: Serum antibodies, ovulation rate, and number of larvae of the parasite Trichinella spiralis.
MHC Summary
- CLASS I:
- Loci: A, B, and C.
- Distribution: Most nucleated cells.
- Function: Present antigen to cytotoxic T cells.
- Result: T cell mediated toxicity.
- CLASS II:
- Loci: DP, DQ, and DR.
- Distribution: B cells, macrophages, and DC.
- Function: Present antigen to T helper cells.
- Result: T-cell mediated help.
MHC History
- The MHC was discovered as a locus containing genes responsible for graft rejection.
- There are two possible outcomes to a skin graft from one animal to another:
- The graft will survive and function.
- The graft will be rejected.
- The Nobel Prize in Physiology or Medicine 1980 was awarded to Baruj Benacerraf, Jean Dausset, and George D. Snell for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions.
The Major Histocompatibility Complex
- The MHC is a region that controlled graft rejection or survival.
- Each MHC cluster of genes has at least 3 classes of the gene loci.
- A typical mammalian MHC has the following arrangement of genes:
- Class I MHC molecules: expressed on all nucleated cells.
- Class II MHC molecules: expressed on antigen presenting cells.
- Class III MHC molecules: do not participate in antigen presentation.
Activation of T Cells
- The main function of T cells is to protect the body against intracellular pathogens and to activate other cells.
- T cells require activation before functioning as effector cells.
- Activation is achieved through interaction of T cells with antigen presenting cells.
- The role of presenting antigen to T cells is performed by specialized proteins called MHC molecules expressed on antigen presenting cells.Here are the study notes in markdown format:
Class I and Class II MHC Molecules
- Found on antigen presenting cells
- Class I: expressed on all nucleated cells, present peptide antigens to CD8+ T lymphocytes
- Class II: expressed on professional antigen presenting cells, present antigens to CD4+ T lymphocytes (helper T lymphocytes)
MHC Genetics
- Each individual has 2 complete sets of MHC molecules, one on each of the paternally and maternally derived chromosomes
- MHC genes are co-dominantly expressed
- Each individual has six MHC I genes (A, B, and C)
- Class II genes give greater diversity due to pairing of different α and β chains
Class I MHC Molecule Structure
- Heterodimer consisting of an α (α1, α2, α3) chain, β2-microglobulin chain, and a bound peptide
- Stable expression requires all three components
- Antigen binding groove is the most variable part of the MHC class I molecule
- CD8 binding region is non-variable
Class II MHC Molecule Structure
- Similarly structured to Class I
- Consists of α (α1, α2) and β (β1, β2) chains
- Peptide binding groove is made up by the α1 and β1 parts of the appropriate chains
- Stable expression requires assembly of the 3 components: the 2 chains and a bound peptide
Peptide-MHC Interactions
- Each class I or class II MHC molecule has a single peptide-binding cleft that binds one peptide at a time
- Each MHC molecule can bind different peptides, so MHC molecules have broad specificity for peptide binding
- T cell receptors (TCRs) have fine specificity for peptide binding
Outcomes of Antigen Presentation
- MHC class I molecules present peptide antigens to CD8+ T lymphocytes
- MHC class II molecules present antigens to CD4+ T lymphocytes (helper T lymphocytes)
MHC and Disease
- The MHC regulates the immune response
- The more variety in an animal's MHC, the more antigens it can respond to
- Heterozygous animals will express more alleles and bind more antigenic peptides
- Homozygous animals will have less variety and may not generate an immune response to certain antigenic peptides
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Description
Learn about the general characteristics of the mammalian MHC, distinguish between class I and class II MHC molecules, understand the role of MHC molecules in immunity, explore the expression profile of MHC molecules on cells, and understand the structure of MHC class I and II. Delve into how certain MHC genes may predispose animals to diseases.