1. Immunology Chapter 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 T H cells can be assayed by –proliferation of T H cells –secretion of various cytokines –ability to activate T C or B cells T C 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  and  chain

5. TCR is a heterodimer Contains  and  chains Constant and variable regions Identified  and  chains –2 - 5% of all T cells Very similar to antibody Variation in amino terminal end

6. Organization and rearrangement of TCR genes The  and  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 (  ) –delta and epsilon chains (  ) –two zeta chains (  ) –zeta and eta chains (  )

9. TCR heterodimer determines binding specificity The CD3 dimers are required for –expression of the TCR –signal transduction The  and  are members of Ig superfamily Both  and  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  heterodimer –both are small glycoproteins of approximately 30 - 38 kDa CD4 binds to the  2 domain of class II CD8 binds to the    of 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)