Podcast
Questions and Answers
What is the chance that two unrelated individuals share HLA identity?
What is the chance that two unrelated individuals share HLA identity?
Which statement correctly describes HLA class II expression?
Which statement correctly describes HLA class II expression?
Which of the following best characterizes HLA genes?
Which of the following best characterizes HLA genes?
In the context of HLA inheritance, what does the term 'homozygous' imply for a child?
In the context of HLA inheritance, what does the term 'homozygous' imply for a child?
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Which option lists HLA class I genes correctly?
Which option lists HLA class I genes correctly?
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What is the significance of HLA polymorphism in relation to disease association?
What is the significance of HLA polymorphism in relation to disease association?
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Which statement best describes the expression of MHC class I proteins?
Which statement best describes the expression of MHC class I proteins?
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What is the primary effect of allelic variation in the α1 and α2 domains of MHC-class I molecules?
What is the primary effect of allelic variation in the α1 and α2 domains of MHC-class I molecules?
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What components form MHC Class I molecules?
What components form MHC Class I molecules?
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Which of the following best explains the role of anchor residues in MHC Class I molecules?
Which of the following best explains the role of anchor residues in MHC Class I molecules?
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Which statement about HLA inheritance is true?
Which statement about HLA inheritance is true?
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In which domains are most polymorphic residues located in MHC Class II molecules?
In which domains are most polymorphic residues located in MHC Class II molecules?
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How does HLA polymorphism contribute to disease association?
How does HLA polymorphism contribute to disease association?
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Which MHC Class II molecule's alpha chain is non-polymorphic?
Which MHC Class II molecule's alpha chain is non-polymorphic?
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What distinguishes the peptide binding of MHC Class I from that of MHC Class II?
What distinguishes the peptide binding of MHC Class I from that of MHC Class II?
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What best describes the expression of MHC proteins?
What best describes the expression of MHC proteins?
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What is the function of the invariant chain in MHC Class II molecule formation?
What is the function of the invariant chain in MHC Class II molecule formation?
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What defines the peptide-binding specificity in different HLA alleles?
What defines the peptide-binding specificity in different HLA alleles?
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Which of the following is not coded by HLA genes?
Which of the following is not coded by HLA genes?
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What is the significance of polymorphism in MHC proteins?
What is the significance of polymorphism in MHC proteins?
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Which processes are involved in the loading of peptides onto MHC Class I molecules?
Which processes are involved in the loading of peptides onto MHC Class I molecules?
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Which of the following is true concerning the interaction of T Cell Receptors (TCRs) with MHC molecules?
Which of the following is true concerning the interaction of T Cell Receptors (TCRs) with MHC molecules?
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What type of antigens does MHC Class II primarily associate with during its processing pathway?
What type of antigens does MHC Class II primarily associate with during its processing pathway?
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HLA polymorphism is associated with susceptibility to which of the following?
HLA polymorphism is associated with susceptibility to which of the following?
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Which of the following characters is correct regarding the variability of peptide binding across different HLA alleles?
Which of the following characters is correct regarding the variability of peptide binding across different HLA alleles?
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Study Notes
Major Histocompatibility Complex (MHC) in Antigen Presentation
- The MHC is a cell surface protein complex that binds to and presents antigenic peptides to T cells.
- MHC genes code for Human Leukocyte Antigens (HLA) proteins.
- Class I and Class II MHC molecules differ in their structure and function, impacting various immunological processes.
Objectives
- Identify MHC genes that code for HLA Class I and Class II molecules.
- Compare and contrast the structure of HLA Class I and Class II molecules.
- Compare and contrast the function of HLA Class I and Class II molecules.
- Compare and contrast HLA Class I and Class II antigen processing and presentation.
- Compare how HLA Class I and Class II genes are expressed on different cell types.
- Understand the role of HLA polymorphism in disease susceptibility and transplant rejection.
The Big Picture of Immune Response
- The immune response involves various cell types including NK, CD4+, and CD8+ T cells and B cells.
- These cells interact through complex mechanisms to eliminate pathogens and maintain immune homeostasis.
The MHC's Role in Antigen Presentation
- Proteins are broken down into peptides by the proteasome within the antigen-presenting cell (APC).
- The peptides then associate with MHC molecules.
- The MHC-peptide complex is displayed on the cell surface.
- T cells recognize this complex and initiate an immune response.
Brief History of MHC Discovery
- MHC was initially discovered in the 1930-1940s in inbred mice via transplantation studies.
- MHC compatibility is crucial for successful transplants and is also crucial for avoiding transplant rejection.
- MHC gene sets are called HLA in humans and H-2 in mice.
MHC: Organization and Classes I, II and III
- MHC proteins are organized into three main classes (Class I, II, and III).
- Class I MHC complex comprises α and ẞ2-microglobulin chain.
- Class II MHC complex comprises α and β chains.
- Class III genes have genes for proteins that are part of the complement system and cytokines.
MHC Class I Molecules
- Composed of an alpha chain and a beta-2 microglobulin molecules.
- Polymorphism exists mostly within the α1 and α2 domains of the peptide-binding groove.
MHC Class II Molecules
- Composed of both alpha and beta chains.
- Allelic variation occurs primarily within the β1 domain.
Inheritance of MHC Genes
- MHC genes are inherited as a set (haplotype) from each parent.
- This leads to a high diversity of MHC proteins across individuals, which can impact immune responses and disease susceptibility.
- HLA coding for the MHC is highly diverse.
HLA-Haplotypes
- Individuals have a high chance of sharing an identical HLA haplotype with closely related family members,.
- HLA haplotypes have a low chance of shared identity between non-related individuals.
MHC Expression on Different Cell Types
- HLA Class I molecules are present on all nucleated cells.
- HLA Class I and II molecules are expressed on professional antigen-presenting cells (APCs).
- HLA Class II expression can be induced by cytokines on some non-professional antigen-presenting cells.
Antigen- Presenting Cell Types
- An antigen-presenting cell (APC) is any cell type that presents antigens to T cells.
- Different APC types present various antigens and interact in different ways with various cell types and situations including inflammation.
MHC and Disease Susceptibility
- Some MHC alleles are linked to a higher risk for specific diseases, like ankylosing spondylitis.
- Some MHC alleles may also influence vaccine responses, like differing responses to certain viral vaccines.
- The MHC's role includes protection against diseases.
Peptide Binding to MHC
- Peptides that bind to different MHC classes are different.
- Peptides are variable even within a singular MHC class.
MHC Class I Antigen Processing Pathway
- Endogenous antigens (inside the APC) are broken down by proteasomes.
- Peptides are transported to the ER by TAP1/2.
- MHC Class I molecules bind to the peptides.
- The MHC-peptide complex is transported to the membrane for presentation to CD8+ T cells.
MHC Class II Antigen Processing Pathway
- Exogenous antigens (from outside the APC) are internalized and degraded into peptides.
- Invariant chain associates with MHCII.
- CLIP (a part of the invariant chain) prevents premature peptide binding.
- HLA-DM catalyzes the exchange of CLIP for antigenic peptides.
- The MHCII-peptide complex is moved to the cell surface for presentation to CD4+ T cells.
B Cells' Role In Antigen Presentation
- B cells can take up foreign antigens and present them within the MHCII.
Cross-Presentation
- Dendritic cells can present exogenous antigens on MHC Class I.
- This allows them to activate cytotoxic T cells
- This is an important way to manage external pathogens.
T Cell Recognition
- T cells recognize the peptide-MHC complex using their T cell receptor (TCR).
- TCR and the MHC-peptide complex is a trimolecular complex.
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