Immunology Chapter 11

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

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

8. 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)

9. 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

10. 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

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

12. 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

13. 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

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