Major Histocompatibility Complex in Immunology
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Questions and Answers

What is the primary function of the Major Histocompatibility Complex (MHC)?

  • To transport oxygen in the blood
  • To degrade proteins within cells
  • To facilitate cell division
  • To present antigenic peptides to T cells (correct)

    • In which situation would the Human Leukocyte Antigen (HLA) be critical?

  • During a bacterial infection
  • For blood clotting
  • In muscle contraction
  • In solid organ transplantation (correct)

    • What determines the ability of a T cell to recognize an antigen?

  • The size of the peptide
  • The combination of MHC and peptide structure (correct)
  • The location of the antigen in the body
  • The presence of antibodies

    • Which class of MHC molecules typically presents antigens to CD4+ T helper cells?

    <p>MHC Class II (A)</p> Signup and view all the answers

    What is the significance of allelic variation in HLA genes?

    <p>It enhances the specificity of immune responses (C)</p> Signup and view all the answers

    Which statement best describes the antigen processing pathway associated with MHC Class I molecules?

    <p>It uses proteasomal degradation of intracellular proteins (A)</p> Signup and view all the answers

    What happens when the T cell receptor (TCR) recognizes an Ag:MHC complex?

    <p>The T cell is activated (D)</p> Signup and view all the answers

    Which gene products are associated with the Human Leukocyte Antigen (HLA) system?

    <p>Both MHC Class I and II proteins (B)</p> Signup and view all the answers

    What domain of MHC Class I molecules primarily undergoes allelic variation?

    <p>α1 and α2 domains (A)</p> Signup and view all the answers

    What is the role of the invariant chain in MHC Class II molecules?

    <p>It acts as a chaperone for MHC Class II synthesis. (B)</p> Signup and view all the answers

    How does allelic variation in HLA molecules relate to clinical outcomes?

    <p>Some HLA alleles are associated with better responses to infections. (B)</p> Signup and view all the answers

    Which process does the proteasome primarily contribute to in the MHC Class I pathway?

    <p>Degrading proteins into peptides. (B)</p> Signup and view all the answers

    What distinguishes the peptide binding between MHC Class I and Class II molecules?

    <p>Class I molecules can bulge longer peptides compared to Class II. (A)</p> Signup and view all the answers

    Which of the following is NOT a step in the formation of MHC Class II molecules?

    <p>Association of α and β chains in the cytoplasm. (A)</p> Signup and view all the answers

    Which statement best describes the effect of anchor residues in MHC Class I molecules?

    <p>They secure peptides in a specific position for T-cell recognition. (A)</p> Signup and view all the answers

    What differentiates HLA-A1 from HLA-A28 in terms of functionality?

    <p>They have different allele-specific pockets for peptide binding. (D)</p> Signup and view all the answers

    Which of the following statements about HLA class I genes is correct?

    <p>They are expressed on all nucleated cells. (A)</p> Signup and view all the answers

    What does a child inherit in terms of HLA haplotypes from parents?

    <p>HLA haplotypes are transmitted as a block. (C)</p> Signup and view all the answers

    Which cytokine is known to induce HLA class II expression on non-professional antigen-presenting cells?

    <p>Interferon-gamma (IFN-γ) (A)</p> Signup and view all the answers

    What is the significance of polymorphism in MHC genes?

    <p>It allows for a wide range of antigen presentation. (A)</p> Signup and view all the answers

    Which of the following combinations is considered a characteristic of HLA class II genes?

    <p>They can be paired in a combinatorial manner. (B)</p> Signup and view all the answers

    What is a key distinguishing feature of beta2 microglobulin (β2m) in the context of MHC?

    <p>It has no polymorphism. (C)</p> Signup and view all the answers

    What is the probability of two siblings sharing HLA identity?

    <p>25% or 1/4 (D)</p> Signup and view all the answers

    Which concept best describes the term 'allele' in the context of MHC genes?

    <p>One of several forms of the same gene. (B)</p> Signup and view all the answers

    Flashcards

    HLA genes

    Genes that influence immune system diversity and disease association.

    HLA-haplotypes

    Sets of HLA genes inherited together from parents.

    HLA identity sharing

    The likelihood of two individuals sharing the same HLA genes.

    HLA class I genes

    Expressed on all nucleated cells, crucial for immune function.

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    HLA class II genes

    Expressed on antigen-presenting cells, critical for immune responses.

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    MHC genes polymorphism

    High genetic variability in MHC genes.

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    MHC genes - polygenic

    Multiple different MHC genes exist.

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    MHC genes - polymorphic

    Many different forms of each MHC gene exist.

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    MHC role in antigen presentation

    MHC proteins bind antigen peptides and display them to T cells.

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    Antigen Presentation Process

    Cells (APCs) break down antigens, bind peptides to MHC proteins, and present the MHC-peptide complex on the cell surface.

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    T cell recognition

    T cells only recognize antigens displayed on MHC molecules.

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    MHC Class I

    One of three major classes of MHC genes that code for cell surface proteins which present peptides to cytotoxic T cells

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    MHC Class II

    One of three major classes of MHC genes that code for cell surface proteins which present peptides to helper T cells.

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    HLA

    Human Leukocyte Antigen; the human equivalent of the MHC.

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    MHC and Transplant Rejection

    Matching MHC genes is crucial for successful organ transplantation; mismatched MHC leads to rejection due to the immune system recognizing foreign protein.

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    T Cell Receptor (TCR)

    A protein on the surface of T cells that recognizes the specific complex of MHC and the Antigen presented on the cell surface of the Antigen presenting cell (APC).

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    HLA-B gene alleles

    There are many different versions (alleles) of the HLA-B gene.

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    MHC Class I molecules

    Proteins that display pieces of proteins made inside the cell (self-antigens)

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    MHC Class II molecules

    Proteins that display pieces of proteins from outside the cell (foreign antigens).

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    Peptide Binding (MHC)

    MHC proteins bind to small protein fragments (peptides) to display them for immune cells.

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    Proteasome

    Cellular machinery that breaks down proteins.

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    Antigen processing

    The process of breaking down proteins and displaying proteins to immune cells.

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    Class I MHC processing

    Process of breaking down endogenous proteins, displaying them to immune system.

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    Class II MHC processing

    Process of breaking down exogenous proteins, displaying them to immune cells.

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    Study Notes

    Major Histocompatibility Complex (MHC) in Antigen Presentation

    • MHC genes code for Human Leukocyte Antigens (HLA)
    • HLA class I and class II genes differ structurally and functionally
    • HLA class I and class II molecules process and present antigens differently
    • HLA class I and II genes are expressed on different cell types
    • HLA polymorphism influences disease susceptibility and transplant rejection
    • MHC proteins are co-dominantly expressed

    The MHC as a Cell Surface Protein

    • MHC is a cell surface protein binding antigenic peptides
    • MHC proteins present peptides to T cells
    • Proteins are degraded by the Antigen-Presenting Cell (APC) or any cell
    • Peptides associate with MHC molecules
    • MHC-peptide complex is expressed on the cell surface
    • A T cell identifies an antigen complexed with MHC
    • Recognition of antigen:MHC activates the T cell

    The Big Picture of Immune Response

    • Primary immune response involves NK cells, CD4+ T cells, CD8+ T cells, B cells
    • Memory B and plasma cells, and Memory CD4 and CD8 T cells are created

    Brief History of MHC

    • MHC was initially discovered as a crucial component in transplant rejection
    • Histocompatibility refers to tissues being compatible
    • MHC genes were studied in genetically identical mice
    • In humans, the same set of genes is known as Human Leukocyte Antigen (HLA)
    • The mice equivalent is the H-2 complex

    Organization of HLA/MHC

    •  HLA/MHC are organized in 3 classes
    • Proteins are generated from genes in the MHC complex
    • HLA class I consists of α chains and β2 microglobulin (ẞ2m)
    • HLA class II comprises an α chain and a β chain
    • Different HLA haplotypes can be present (gene variants)
    • HLA-DP, HLA-DQ, and HLA-DR are MHC class II genes
    • Most polymorphic residues are found within the peptide-binding groove

    MHC on APC and TCR

    • MHC molecule on Antigen Presenting Cell (APC) presents antigen to T cell receptor
    • T cell receptors (TCRs) recognize the MHC-peptide complex
    • This interaction structure is comparable to a lock and key

    Structure of MHC Proteins

    • MHC proteins are transmembrane proteins
    •  The structure resembles immunoglobulins (Abs)

    MHC Class I Molecules

    • MHC class I molecules are formed by an alpha chain and beta-2 microglobulin
    • HLA-A, HLA-B, and HLA-C alleles encode alpha chains
    • 2 m is essential for HLA class I expression

    MHC Class II Molecules

    • HLA-DP, HLA-DQ, and HLA-DR alleles encode class II molecules
    • HLA-DR alpha and beta chains are polymorphic

    Proteins and Peptides in MHC

    • Proteins that are degraded into peptides are loaded onto MHC molecules
    • Proteasome processes endogenous proteins into peptides
    • TAP1/2 is responsible for peptide transportation into endoplasmic reticulum (ER)

    MHC Class II - Exogenous Antibody Pathway

    • Class II MHC formation: α and β chains are synthesized and combined with invariant chain (Ii) in the endoplasmic reticulum
    • Invariant chain to a placeholder that is degraded into CLIP (small peptide)
    • Peptides are produced from the exogenous antigen that is taken up by the APC, then degraded in acidic vesicles
    • CLIP exchange: MHC-peptide complex is formed by replacing CLIP with a peptide, mediated by HLA DM
    • Peptides bind to MHC molecules in MHC-peptide complex form

    MHC Antigen Binding - Binding Differences

    • The peptides that bind to class I MHC are different from those that bind to class II MHC

    Cross-Presentation

    • Dendritic cells transfer exogenous antigens to MHC class I molecules
    • This allows them to activate cytotoxic T cells using antigens from outside the cell

    MHC and Diseases

    • Some HLA alleles are linked to increased risks for certain diseases
    • HLA variation results in differing responses to vaccines

    Recognition of Peptide:MHC by T Cell

    • Recognition of peptide bound to MHC by T cells initiates the adaptive immune response
    • Two main types of T cells: CD4+ T-helper and CD8+ cytotoxic T cells
    • The T cell receptor (TCR) interacts with the Peptide:MHC to drive an adaptive immune response

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    Description

    Explore the essential role of Major Histocompatibility Complex (MHC) in antigen presentation and the immune response. This quiz covers the structure and function of HLA class I and II molecules, their expression on different cell types, and how they interact with T cells. Test your understanding of immune mechanisms and the significance of MHC in disease susceptibility.

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