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Questions and Answers
What is the main role of MHC Class I proteins in the immune response?
What is the main role of MHC Class I proteins in the immune response?
Which cells typically express MHC Class II proteins?
Which cells typically express MHC Class II proteins?
What is the chromosome localization of MHC genes in humans?
What is the chromosome localization of MHC genes in humans?
What is the size of peptides presented by MHC Class I proteins?
What is the size of peptides presented by MHC Class I proteins?
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Which function is NOT associated with MHC genes?
Which function is NOT associated with MHC genes?
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What is meant by MHC haplotypes?
What is meant by MHC haplotypes?
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Which of the following describes MHC Class II proteins?
Which of the following describes MHC Class II proteins?
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What is a primary feature of MHC gene expression?
What is a primary feature of MHC gene expression?
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What are the two types of polypeptide chains that compose Class II MHC proteins?
What are the two types of polypeptide chains that compose Class II MHC proteins?
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Which of the following correctly describes the peptide-binding clefts in MHC class I and II proteins?
Which of the following correctly describes the peptide-binding clefts in MHC class I and II proteins?
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In terms of peptide length, how do peptides bind to MHC class I molecules?
In terms of peptide length, how do peptides bind to MHC class I molecules?
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What is a key characteristic of the anchor residues in peptides binding to MHC class I molecules?
What is a key characteristic of the anchor residues in peptides binding to MHC class I molecules?
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Why is self MHC restriction important for T cell functionality?
Why is self MHC restriction important for T cell functionality?
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What role do CD4+ helper T cells play in the immune response?
What role do CD4+ helper T cells play in the immune response?
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How many anchor residues are typically found in the central region of peptides binding to MHC class II molecules?
How many anchor residues are typically found in the central region of peptides binding to MHC class II molecules?
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What distinguishes the binding of antigens by cytotoxic T cells from helper T cells?
What distinguishes the binding of antigens by cytotoxic T cells from helper T cells?
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Study Notes
Introduction to Major Histocompatibility Complex (MHC)
- MHC molecules are crucial for immunity
- Understanding MHC structure and function is fundamental to immunology
- MHC molecules present antigens to T cells
Learning Objectives
- Understand the structure and function of MHC molecules
- Understand the genetics of MHC and MHC restriction in T cell activation
How is MHC related to immunity?
- Antibodies recognize antigens alone
- T-cell receptors recognize antigens processed and presented by MHC
- MHC involves antigen processing and presentation
MHC
- MHC is a complex of genes on chromosome 6 in humans and chromosome 17 in mice
- MHC spans 4-7 million base pairs (bp)
- MHC has over 200 genes in 4 regions (Class I, Class Ib, Class II, and Class III)
- MHC products mediate T-cell development, antigen recognition, graft rejection, and susceptibility to diseases
Chromosome 6: HLA region
- HLA region is part of chromosome 6
- HLA region includes Class I, Class II, and Class III genes
MHC
- MHC Class I and Class II proteins present peptide fragments to T cells
- MHC protein with bound peptide is a ligand for the T-cell receptor (TCR)
- CD8+ T cells bind to MHC Class I:peptide complexes
- CD4+ T cells bind to MHC Class II:peptide complexes
Class I MHC Genes
- Involved in immune responses against endogenous antigens (inside cells)
- Typically found in virally infected or tumor cells
- Presents 8-10 amino acid peptides recognized by cytotoxic T cells
- Found in all nucleated cells
Class II MHC Genes
- Involved in immune responses against exogenous antigens (outside cells)
- Found on cells like B lymphocytes, macrophages, monocytes, dendritic cells, and endothelial cells
- These cells are phagocytic and engulf external antigens
- MHC Class II proteins present 13-18 amino acid peptides recognized by T helper cells
MHC Haplotypes
- Set of genes on a single chromosome with characteristics dependent on the genes
- Each individual has 2 haplotypes (maternal and paternal) for each set of genes
- MHC genes are co-dominantly expressed (both maternal and paternal products in the same cells)
Class I MHC Proteins
- Composed of two polypeptide chains: an alpha chain (transmembrane) and a beta-2 microglobulin chain (encoded on a different chromosome)
- Composed of a folded molecule with 4 domains (a1, a2, a3, β2) and a peptide-binding cleft (created by a1 and a2)
Class II MHC Proteins
- Composed of two polypeptide chains: an alpha chain and a beta chain (Both transmembrane)
- Composed of a folded molecule with 4 domains (alpha 1, alpha 2, beta 1, beta 2)and a peptide-binding cleft (created by a1 and β1)
MHC Proteins
- Peptide Binding Cleft is similar in Class I and Class II
- The floor of the cleft is a β sheet
- The walls of the cleft are α helices
- Class I clefts are closed, while Class II clefts are open
- Peptides are within the clefts in an extended conformation
MHC Peptide Binding to Class I
- Selectively binds to certain peptides with high affinity
- Peptides are 8-9 amino acids long
- Aliphatic or aromatic residues act as "anchors" for peptides within the cleft
- Anchor residues are common in all peptides bound to a particular MHC Class I molecule
MHC Peptide Binding to Class II
- Binds to peptides of variable length (12-17 amino acids)
- Three or four anchor residues within the central region of the peptide bind to allele-specific pockets of the MHC class II protein
- MHC class II proteins bind to a wide range of peptides, and anchor residue prediction is challenging
Self MHC Restriction
- T-cells only recognize and respond to antigenic peptides combined with MHC molecules
- Helper T-cells recognize antigens in the context of class II self MHC
- Cytotoxic T-cells recognize antigens in the context of class I self MHC
Self MHC Restriction of Tc Cells
- Tc cells only kill syngeneic virally infected target cells
- Both Tc cells and infected cells must share the same MHC
Summary
- Understanding MHC is fundamental for immunology
- MHC class I molecules present endogenous antigens to CD8+ cytotoxic T-cells
- MHC class II molecules present exogenous antigens to CD4+ helper T-cells
- MHC restriction ensures that T-cells only respond to foreign antigens presented by the body's own MHC molecules
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Description
This quiz covers the structure and function of Major Histocompatibility Complex (MHC) molecules, which are essential for immune responses. You will learn about MHC's role in presenting antigens to T cells, its genetics, and its impact on immunity and disease. Understanding MHC is fundamental for students of immunology.
