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Direct and Indirect Alloantigen Recognition

by Peter Delves, PhD
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    Rejection can be due either to a direct or an indirect alloantigen recognition. In direct alloantigen recognition, the allogeneic antigen presenting cell in the graft shows the allogeneic MHC to a alloreactive T-cell. The T-cell in the recipient recognizes unprocessed allogeneic MHC molecules on the graft APC. So the graft from the donor will most often have some foreign MHC molecules. It’s almost impossible to completely match between the donor and the recipient across all of the MHC molecules. Remember there will be six different MHC Class I’s, six different MHC Class II’s. So matching perfectly is incredibly difficult and incredibly rare. So usually there will be this recognition of allogeneic MHC, and here we see it occurring in a direct way where the recipient’s T-cells directly recognize the foreign MHC on the donor cells. There is also indirect alloantigen presentation which occurs. This is due to uptake and processing of the allogeneic MHC molecules by the recipient’s antigen presenting cells. And peptides derived from the allogeneic MHC molecule are shown to the T-cells in the recipient. So there is presentation of processed peptide of the foreign allogeneic MHC molecule bound to the recipient’s own self MHC molecules. So fragments of the foreign MHC being shown by the recipient’s MHC to the T-cell receptor on their T-cells. And both of these processes take place following transplantation unless there is an absolutely perfect match. Let us now look at the activation of alloreactive T-cells. There will be a sensitization phase, where the donor dendritic cells and recipient dendritic cells will show donor alloantigen to T-cells. There’ll be transport of those alloantigens to the lymph nodes with activation of T-cells. The generation of effector T-cells in the recipient by both the direct and indirect antigen presentation pathways that we’ve just explored. And...

    About the Lecture

    The lecture Direct and Indirect Alloantigen Recognition by Peter Delves, PhD is from the course Transplantation Immunology. It contains the following chapters:

    • Direct and Indirect Alloantigen Recognition
    • Activation of Alloreactive T-Cells
    • The Immune Response to a Liver Graft

    Included Quiz Questions

    1. IL-2
    2. IL-4
    3. IL-10
    4. IL-12
    5. IL-13
    1. Allogeneic antigen presenting cells that express allogeneic MHC
    2. Autoreactive T-cells
    3. Memory T cells specific for allograft
    4. Allogeneic antigen presenting cells that express self MHC
    5. Self antigen presenting cells that express allogeneic MHC
    1. T cells become activated and CD4+ and CD8+ effector T cells targeting the alloantigen are produced
    2. Allogeneic effector T cells secrete cytokines which induce graft rejection
    3. CD4+ effector T cells become activated and travel to allograft- CD8+ cells are not involved
    4. Allogeneic APCs will activate self CD4+ effector T cells, mediating graft rejection
    5. Cytokines produced by allogeneic CD4+ cells will prevent invasion of CD4+ and CD8+ effector T cells from host
    1. Treg cells
    2. Complement activation
    3. IL-2
    4. IFNγ
    5. IL-1

    Author of lecture Direct and Indirect Alloantigen Recognition

     Peter Delves, PhD

    Peter Delves, PhD


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