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Gamma-Delta T-Cells, T-Cell Receptor and Alpha-Beta T-Cells – Cell-Mediated Immunity

by Peter Delves, PhD
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    00:01 Let’s just spend a couple of moments to look at gamma-delta (γδ) T-cells, and exactly what they do and what they are.

    00:09 They appear to have a distinct role that is complementary to that of the alpha-beta (αβ) T-cells.

    00:16 They comprise less than five percent of the T-cells.

    00:19 So they’re very much a minority population of T-cells.

    00:22 And they’re present mostly in the gut mucosa, in the skin, in the lungs and in the uterus.

    00:29 And they can directly recognize microbial pathogens, and also damaged or stressed host cells.

    00:35 In other words, our own cells that are damaged due to infection or other types of pathology.

    00:42 To give you just a couple of examples of the recognition that can occur by γδ T-cells.

    00:48 You can have direct recognition of phosphoantigens from Mycobacterium tuberculosis, from Plasmodium malariae without any requirement for antigen processing whatsoever.

    01:03 And there can be direct recognition of the MHC-like non-peptide-binding molecules, MICA and MICB, or of CD1 irrespective of any lipoprotein or glycolipid antigen.

    01:18 So they can recognize structures that are coming from foreign pathogens, but they can also recognize our own molecules that are upregulated in response to stress or other events.

    01:29 Here’s the structure of the T-cell receptor on the surface of a T-lymphocyte.

    01:34 It’s a heterodimer, consists of two chains.

    01:38 And here we can see the αβ T-cell receptor.

    01:42 The γδ T-cell receptor looks almost identical.

    01:49 In both cases, the two chains of the T-cell receptor are linked together by a disulfide bond.

    01:56 There are transmembrane segments associated with both chains of the T-cell receptor.

    02:02 Each chain is folded into two domains; a Variable domain which is stabilized by an intra-chain disulfide bond, and a Constant domain also stabilized by an intra-chain disulfide bond.

    02:17 Looking at exactly how the T-cell receptor interacts with peptide MHC; at the top of this diagram, we can see the two Variable domains of the T-cell receptor.

    02:31 Underneath is the MHC Class I α-chain.

    02:37 This is associated with β2-microglobulin.

    02:42 And then sitting between the α-helices of the MHC Class I α-chain is the antigenic peptide.

    02:51 And this is making contact not only with the MHC but also with the hypervariable or CDR regions of both the α-chain and the β-chain of the T-cell receptor Variable regions.

    03:06 αβ T-cells, are not all the same. There’s a variety of different types of αβ T-cells. So let us look at the different types.

    03:16 Well, there are ones that have CD4 on their cell surface and there are others that have CD8 on their cell surface.

    03:23 So that’s one distinction.

    03:25 Within the CD4+ αβ T-cells, there are a number of subpopulations - Th1, Th2, Th17, T-follicular helper and T-regulatory cells amongst others.

    03:41 These are the most important, or at least the best characterized at this point in time.

    03:49 They can be distinguished by a number of different features.

    03:53 So if we look at the transcription factors that are expressed in the nucleus of these different types of T-cell, we see that Th1 cells express the transcription factors T-bet and STAT4.

    04:09 They produce a variety of different cytokines - gamma interferon, interleukin-2, tumor necrosis factor beta.

    04:18 These are typical cytokines that are produced by Th1 cells.

    04:22 And in fact, the first distinction of these different types of helper T-cells was based upon the particular cytokines that they produced.

    04:31 The primary function of Th1 cells is to help cytotoxic T-lymphocytes and to help macrophages.

    04:39 Although, they can also help some B-cells to produce antibody.

    04:42 Importantly, they can inhibit the activity of Th2 cells.

    04:48 Turning now to Th2 cells, they express the transcription factors GATA3 and STAT6 in their nucleus.

    04:55 They produce the cytokines interleukin-4, IL-5, IL-6 and IL-13.

    05:01 And their primary function is to help B-cells.

    05:05 Importantly, just like Th1 cells can inhibit Th2 cells, so Th2 cells can inhibit Th1 cells.

    05:13 So these two populations, Th1 and Th2, at least to some extent are mutually antagonistic towards each other.

    05:22 Th17 cells express the transcription factor RORγt in the nucleus.

    05:28 And as their name suggests, they produce interleukin-17, amongst other cytokines such as interleukin-22.

    05:36 And these cells are really specialized to promote inflammation.

    05:41 T-follicular helper cells are cells that are found in the germinal centers of secondary lymphoid tissues where they assist in the activation of B-lymphocytes.

    05:53 They express the transcription factor Bcl-6.

    05:56 And they produce cytokines such as interleukin-21 and ICOS.

    06:02 And as I’ve already mentioned, their function is to help germinal center B-cells.

    06:05 So those four cell types all enhance immune responses, they help immune responses.

    06:12 In contrast, T-regulatory cells suppress immune responses.

    06:17 And they express the transcription factor Foxp3 in their nucleus, very characteristic transcription factor of regulatory T-cells.

    06:26 The cytokines they produce tend to be cytokines that overall have immunosuppressive activity.

    06:34 Cytokines such as transforming growth factor beta, interleukin-10 and interleukin-35.

    06:40 And again as I’ve already mentioned, the primary function of T-regs is to suppress immune responses.

    06:47 So those are different types of CD4+ αβ T-cells.

    06:51 What about the CD8s? Well, these are generally cytotoxic T-lymphocytes.

    06:57 And they express in their nucleus, the transcription factor RUNX3.

    07:03 They function by producing molecules such as perforin, granzymes, Fas ligand, but they can also produce a variety of cytokines.

    07:14 And their role is to kill infected cells.


    About the Lecture

    The lecture Gamma-Delta T-Cells, T-Cell Receptor and Alpha-Beta T-Cells – Cell-Mediated Immunity by Peter Delves, PhD is from the course Humoral Immunity and Cell-Mediated Immunity. It contains the following chapters:

    • A Closer Look on Gamma-Delta T-Cells
    • Structure of the T-Cell Receptor
    • A Closer Look on Alpha-Beta T-Cells

    Included Quiz Questions

    1. T-bet
    2. STAT6
    3. RORγt
    4. Bcl-6
    5. RUNX3
    1. Bcl-6
    2. Phosphoantigens from M. tuberucolsis
    3. Phosphoantigens from P. malariae
    4. CD1
    5. MICA or MICB
    1. MHC alpha helices, CDR the of the T cell variable regions
    2. MHC beta-globulin, T cell hypervariable regions
    3. MHC beta-globulin, CDR of the T cell variable regions
    4. MHC alpha helices, T cell alpha and beta chain constant regions
    5. MHC alpha helices, CDR of the T cell constant regions
    1. Th1, Th2, and Treg
    2. Th1, Th17, and Treg
    3. Th2, Tfh, and Treg
    4. Th1, Th2, and Tfh
    5. Th2, Th17, and Tfh

    Author of lecture Gamma-Delta T-Cells, T-Cell Receptor and Alpha-Beta T-Cells – Cell-Mediated Immunity

     Peter Delves, PhD

    Peter Delves, PhD


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    By Hernando J. on 20. April 2017 for Gamma-Delta T-Cells, T-Cell Receptor and Alpha-Beta T-Cells – Cell-Mediated Immunity

    Makes it way more easier to understand, it is very summarized and clear.