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Polymorphism and TCR Recognition of Major Histocompatibility Complex – Antigen Processing and Presentation

by Peter Delves, PhD
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    So these molecules vary hugely from one individual to another. We call them polymorphic. In fact the MHC genes are the most polymorphic genes in the whole of the human genome. So why is that? Why do they vary so much from one individual to another? Well the most likely reason is that during evolution, they have diversified so that at least at a population level, there is a huge diversity of MHC that is able to present to T-cells almost any pathogen that might arise during evolution. So, evolution is worried more about the population level than the individual. So it may be that your MHC molecules may not present peptides from a certain virus, but other people’s will. At the tip of the MHC molecule, there is a peptide binding groove that binds the peptide. And as you can see, in the peptide binding groove there is a beta (β)-sheet floor and there are alpha (α)-helices. And the β-sheet floor and the two α-helices are the bits that vary from one individual to another, and between the different MHC molecules. And the same is true for MHC Class II; β-sheet floor and the α-helices are the polymorphic regions that bind the peptide. However there are also non-polymorphic regions, not associated with the peptide binding groove. And they are important in the binding of other molecules to MHC. So for example, the molecule CD8 binds to non-polymorphic regions of MHC Class I whereas the molecule CD4 binds to non-polymorphic regions of MHC Class II. The fact that the T-cell receptor has to recognize a combination of peptide MHC which we can abbreviate to a lowercase pMHC, ensures cell-cell contact. So here we can see an MHC Class I molecule presenting peptides. And this is going to present those peptides...

    About the Lecture

    The lecture Polymorphism and TCR Recognition of Major Histocompatibility Complex – Antigen Processing and Presentation by Peter Delves, PhD is from the course Adaptive Immune System. It contains the following chapters:

    • Polymorphism of MHC
    • TCR Recognition of Peptide-MHC

    Included Quiz Questions

    1. ...a non-polymorphic part of MHC class I.
    2. ...a polymorphic part of MHC class I.
    3. ...a non-polymorphic part of MHC class II.
    4. ,,,a polymorphic part of MHC class II.
    5. ...a non-polymorphic part of both MHC class I and MHC class II.
    1. ...alpha-helices and beta-sheet floor of the peptide binding groove.
    2. ...beta-helices and alpha-sheet floor of the peptide binding groove.
    3. ...alpha-helices and beta-sheet floor of CD4 and CD8 binding sites.
    4. ...adjacent to non-polymorphic regions, where chemokines bind to the molecule.
    5. ...peptide binding groove where CD4 and CD8 bind.
    1. MHC class I, because MHC I binds to CD8 on cytotoxic T cells
    2. MHC class I, because MHC I binds to CD4 on cytotoxic T cells
    3. MHC class I, because MHC I binds to CD8 on helper T cells
    4. MHC class II, because MHC II binds to CD8 on cytotoxic T cells
    5. MHC class II, because MHC II binds to CD4 on Th2 cells
    1. ...The release of cytokines from Helper T cells or Regulatory T cells.
    2. ...the release of cytotoxic complement molecules which destroy immune response cells.
    3. ...the inactivation of T cell response when CD4 is bound to MHC II molecules in the presence of costimulation.
    4. ...the irreversible binding to T cells mediated by CD4.
    5. ...the ability to revert activated T cells back to naive T cells.

    Author of lecture Polymorphism and TCR Recognition of Major Histocompatibility Complex – Antigen Processing and Presentation

     Peter Delves, PhD

    Peter Delves, PhD


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