Podcast
Questions and Answers
What is the primary role of MHC molecules in the immune response?
What is the primary role of MHC molecules in the immune response?
- Producing antibodies against infections
- Facilitating intercellular recognition and discrimination between self and non-self (correct)
- Directly destroying pathogens
- Regulating blood cell production
Which class of MHC molecules is primarily involved in presenting antigens to TC cells?
Which class of MHC molecules is primarily involved in presenting antigens to TC cells?
- Class I MHC molecules (correct)
- Class II MHC molecules
- Class III MHC molecules
- Nonclassical MHC molecules
Which of the following cell types predominantly expresses class II MHC molecules?
Which of the following cell types predominantly expresses class II MHC molecules?
- Red blood cells
- Muscle cells
- B cells (correct)
- Neurons
What distinguishes nonclassical class I MHC molecules from classical class I molecules?
What distinguishes nonclassical class I MHC molecules from classical class I molecules?
Where is the MHC located in humans?
Where is the MHC located in humans?
What type of glycoproteins are encoded by class I MHC genes?
What type of glycoproteins are encoded by class I MHC genes?
Which MHC class molecules are known to interact primarily with TH cells?
Which MHC class molecules are known to interact primarily with TH cells?
What role do classical class I MHC molecules primarily serve in the immune system?
What role do classical class I MHC molecules primarily serve in the immune system?
What type of peptides do class I MHC molecules primarily present to CD8 T cells?
What type of peptides do class I MHC molecules primarily present to CD8 T cells?
Which domains form the peptide-binding cleft in class I MHC molecules?
Which domains form the peptide-binding cleft in class I MHC molecules?
What happens to viral peptides in infected cells concerning class I MHC molecules?
What happens to viral peptides in infected cells concerning class I MHC molecules?
Where are class I MHC molecules primarily expressed?
Where are class I MHC molecules primarily expressed?
What is the primary role of HLA-G molecules at the fetal-maternal interface?
What is the primary role of HLA-G molecules at the fetal-maternal interface?
Which statement about the structure of class I MHC molecules is true?
Which statement about the structure of class I MHC molecules is true?
How many copies of each class I MHC molecule does a single nucleated cell typically express?
How many copies of each class I MHC molecule does a single nucleated cell typically express?
What is the significance of the unique set of peptides bound by each type of class I MHC molecule?
What is the significance of the unique set of peptides bound by each type of class I MHC molecule?
What is the primary reason that MHC molecules can present a vast array of antigenic peptides to T cells?
What is the primary reason that MHC molecules can present a vast array of antigenic peptides to T cells?
What is the typical length of peptides bound to class I MHC molecules?
What is the typical length of peptides bound to class I MHC molecules?
Which statement accurately describes the diversity of MHC molecules within an individual?
Which statement accurately describes the diversity of MHC molecules within an individual?
What defines the binding characteristics of peptides to class II MHC molecules?
What defines the binding characteristics of peptides to class II MHC molecules?
What is significant about the inheritance of MHC alleles from parents?
What is significant about the inheritance of MHC alleles from parents?
Which cells typically express class II MHC molecules?
Which cells typically express class II MHC molecules?
How does the recombination frequency within the MHC loci impact inheritance?
How does the recombination frequency within the MHC loci impact inheritance?
What type of proteins are most peptides associated with class II MHC molecules derived from?
What type of proteins are most peptides associated with class II MHC molecules derived from?
What mechanism ensures that MHC molecules are fixed and do not change over time within an individual?
What mechanism ensures that MHC molecules are fixed and do not change over time within an individual?
Which characteristic differentiates MHC molecule binding from antibody binding?
Which characteristic differentiates MHC molecule binding from antibody binding?
How do anchor residues function in the binding of peptides to class I MHC molecules?
How do anchor residues function in the binding of peptides to class I MHC molecules?
What role does polymorphism play in the diversity of MHC molecules?
What role does polymorphism play in the diversity of MHC molecules?
What distinguishes the socket-like structure of class I MHC molecules from the shape of class II MHC molecules?
What distinguishes the socket-like structure of class I MHC molecules from the shape of class II MHC molecules?
Which of the following statements about class II MHC peptide binding is TRUE?
Which of the following statements about class II MHC peptide binding is TRUE?
How often does crossover occur within the H-2 complex during mitosis?
How often does crossover occur within the H-2 complex during mitosis?
Which polypeptide chains are present in class II MHC molecules?
Which polypeptide chains are present in class II MHC molecules?
What dictates whether an antigenic peptide associates with class I or class II molecules?
What dictates whether an antigenic peptide associates with class I or class II molecules?
What mechanism prevents class II MHC molecules from binding to the same set of antigenic peptides as class I molecules?
What mechanism prevents class II MHC molecules from binding to the same set of antigenic peptides as class I molecules?
How do macrophages internalize antigens?
How do macrophages internalize antigens?
What is the role of the HLA-DM molecule in antigen processing?
What is the role of the HLA-DM molecule in antigen processing?
What happens to the invariant chain during the transport of class II MHC–invariant chain complexes?
What happens to the invariant chain during the transport of class II MHC–invariant chain complexes?
How many different class I and class II MHC molecules can an individual express?
How many different class I and class II MHC molecules can an individual express?
What is the significance of CLIP in the context of class II MHC molecules?
What is the significance of CLIP in the context of class II MHC molecules?
What condition does HLA-DO impose on the class II antigen processing?
What condition does HLA-DO impose on the class II antigen processing?
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Study Notes
MHC Structure and Function
- Major Histocompatibility Complex (MHC) is a cluster of genes that play a critical role in immune responses.
- MHC genes are located on chromosome 6 in humans (HLA complex) and chromosome 17 in mice (H-2 complex).
- MHC genes are divided into three classes: Class I, Class II, and Class III.
- Class I MHC molecules:
- Expressed on nearly all nucleated cells.
- Present peptides from the cytosol (endogenous pathway) to CD8+ T cells.
- Composed of an α chain and β2-microglobulin.
- α chain has three external domains (α1, α2, α3), a transmembrane domain, and a cytoplasmic anchor segment.
- α1 and α2 domains form a peptide-binding cleft.
- Peptides bound by Class I molecules are typically 8-10 amino acids long.
- Class II MHC molecules:
- Primarily expressed on antigen-presenting cells (APCs) like macrophages, dendritic cells (DCs), and B cells.
- Present peptides from exogenous proteins (endocytic pathway) to CD4+ T cells.
- Composed of two polypeptide chains: α chain and β chain.
- Each chain has two external domains (α1, α2, β1, β2).
- α1 and β1 domains form the antigen binding cleft.
- Class III MHC molecules:
- A group of unrelated proteins involved in immune responses, but not directly involved in antigen presentation.
MHC Polymorphism
- MHC genes are highly polymorphic, meaning they exist in many different versions (alleles) within a population.
- This polymorphism creates a diverse repertoire of MHC molecules, allowing the immune system to recognize a vast array of antigens.
- Individuals inherit one set of MHC alleles (haplotype) from each parent.
- Both maternal and paternal MHC alleles are expressed in the same cells (codominant expression).
MHC Expression and Function
- Class I MHC expression:
- High in lymphocytes, low in fibroblasts, muscle cells, liver hepatocytes, and neural cells.
- The low expression in liver cells helps to prevent rejection of transplanted livers.
- Class II MHC expression:
- Constitutively expressed only by APCs.
- Invariant chain (Ii):
- Associates with Class II MHC molecules in the endoplasmic reticulum (ER) to prevent premature binding of peptides.
- Degraded sequentially as the Class II-Ii complex moves through the endocytic pathway.
- CLIP:
- A fragment of Ii that remains bound to the peptide-binding groove of Class II MHC molecules.
- Exchanged for antigenic peptides by the nonclassical Class II molecule HLA-DM.
MHC and Immune Response
- Different MHC alleles have slightly different peptide-binding specificities.
- MHC molecules can bind and present a diverse range of peptides, contributing to the ability of the immune system to recognize a wide variety of antigens.
- MHC molecules are relatively stable and do not change over time in an individual, unlike the diversity of antibodies and T cell receptors.
- The genetic diversity of MHC within a species is a critical factor in the ability of the immune system to respond effectively to pathogens.
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