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Immunology Chapter 11

This chapter explores the T-cell receptor (TCR), a crucial element in the immune system. The TCR, a cell-surface molecule, recognizes antigens in conjunction with MHC, distinguishing it from mere antigen specificity. The structure of TCR includes alpha and beta chains, forming a heterodimer, and is associated with the CD3 complex for signal transduction. It discusses the genetic organization and rearrangement of TCR genes, the roles of accessory molecules like CD4 and CD8, and the functional assays used to study T-cell activation and differentiation.

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Immunology Chapter 11

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  1. ImmunologyChapter 11 • Richard L. Myers, Ph.D. • Department of Biology • Southwest Missouri State • Temple Hall 227 • Telephone: 417-836-5307 • Email: rlm967f@mail.smsu.edu • Homepage: http://creative.smsu.edu/biology/myersr/index.html • TopClass: http://creative.smsu.edu

  2. T cell receptor • Nature of the T cell receptor (TCR) recently discovered • T cell receptor is a cell-surface molecule • TCR is not specific for antigen alone, but rather antigen in association with an MHC • TCR studied with monoclonal antibodies and nucleic acid probes

  3. Functional assays for TCR • TH cells can be assayed by • proliferation of TH cells • secretion of various cytokines • ability to activate TC or B cells • TC cells can be assayed by • lysis of target cells • secretion of cytokines

  4. Structure of T cell receptor • Experimental approaches assumed that there should be a significant difference in the TCR from clone to clone • Kappler and Marrack • used clonotypic monoclonal antibodies • identified and isolated the TCR • These researchers and others showed the molecule is composed of an a and b chain

  5. TCR is a heterodimer • Contains a and b chains • Constant and variable regions • Identified d and g chains • 2 - 5% of all T cells • Very similar to antibody • Variation in amino terminal end

  6. Organization and rearrangement of TCR genes • The ab and gd TCRs are expressed only in T cells • The genes for these are very similar to the multigene organization of the Ig genes • Separate V, D, and J gene segments rearrange during T cell maturation • Genes composed of introns and exons • Rearrangements produce more antigenic specificities than antibodies

  7. T cell receptor complex • The TCR associates with CD3 • forms a TCR-CD3 membrane complex • The CD3 (accessory molecule) is involved in signal transduction after seeing antigen • CD3 is a complex of 5 invariant chains that form heterodimers • gamma and epsilon chains (ge) • delta and epsilon chains (de) • two zeta chains (zz) • zeta and eta chains (zh)

  8. TCR heterodimer determines binding specificity • The CD3 dimers are required for • expression of the TCR • signal transduction • The g, d, and e are members of Ig superfamily • Both z and h are different

  9. T cell accessory membrane molecules • Recognition of an antigen-MHC complex is mediated by the TCR-CD3 complex • A variety of accessory membrane molecules play a role in recognition and activation • many are adhesion molecules • strengthen the interaction between the two cells • transduce signals through the membrane • some are members of the Ig superfamily

  10. T cells possess several molecules • CD2 • LFA • others • These bind to ligands on APCs or target cells • Strengthen the association between these cells

  11. CD4 and CD8 coreceptors • Both CD4 and CD8 play an dual function • adhesion molecules • co-signaling receptors • CD4+ T cells recognize antigen with class II MHC molecules • CD8+ T cells recognize antigen with class I MCH molecules

  12. CD4 is a 55 kDa monomeric membrane glycoprotein • has 4 extracellular domains • CD8 is a disulfide-linked ab heterodimer • both are small glycoproteins of approximately 30 - 38 kDa • CD4 binds to the b2 domain of class II • CD8 binds to the a3of a class I • They react with the same MHC molecule that reacts with the TCR

  13. Assignment • Read Chapter 12, T-Cell Maturation, Activation and Differentiation • Review question 1 (pg 309)

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