T Cell Receptor

1. T Cell Receptor Hugh B. Fackrell Nov 9, 1998

2. T Cell Receptor • Assigned Reading • Content Outline • Performance Ojectives • Key terms • Key Concepts • Short Answer Questions

3. Assigned Reading • Chapter: 11 pp 264-283 • Janis Kuby’s Immunology 3rd Ed

4. Early Studies Structure of T cell Receptors TCR Genes Cloning TCR multi gene families T Cell Receptor Complex TCR-Peptide-MHC Complex Associative recognition hypothesis Formation of ternary complex Alloreactivity of T Cells Content Outline

5. Early Studies • self MHC restriction • isolation of t cell receptors

6. Independent vs Associative Recognition by T cells

8. Evidence for Altered Self Model

9. Hetero dimer 95% Alpha: Beta 2-5% Gamma: Delta Variable Domains 3 HVR Constant Domains Transmembrane region (Tm) ~20 AA Cytoplasmic Tail (CT) 5-12 amino acids TCR: Structure

10. Structure of T cell Receptors

11. Cloning TCR Genes DNA subtractive hybridization

12. TCR Genes

13. TCR multi gene families: Outline • Variable region rearrangements • TCR DNA rearrangements • Allelic exclusion • Structure of rearranged TCR genes • Generation of TCR diversity

14. TCR Multigene Families: General • 4 multigene families • one for each chain • Gene rearrangements • Alpha: Gamma - V J exons • Beta: Delta - V D J exons • Chain exclusion

15. TCR Gene Rearrangement

16. TCR vs Ig

19. T Cell Receptor Complex • CD4 & CD8 coreceptors • Accessory membrane molecules

20. TCR-Peptide-MHC Complex

22. Associative recognition hypothesis • Formation of ternary complex • Affinity of TCR • Peptide topology

23. Alloreactivity of T Cells

24. Performance Objectives

25. Key Terms • CD2, CD4, CD8, CD28, CD54, CD58, integrins, T cell receptors, • alpha beta TCR, gamma delta TCR, Transcription factor • NF-KB

26. Key Concepts • Draw the structure of the T Cell Receptor (TCR) • Compare and constrast the structure of TCR with B cell receptor • Draw a diagram of the T cell receptor gene organization

27. Describe the stragetgies for diversification of T Cell Receptors • Describe how a T cell Receptor recognizes an antigen • Describe the TCR-Antigen-MHC complex

28. Short Answer Questions

29. Hedrick and Davis used the technique of subtractive hybridization to isolate cDNA clones encoding for the T cell receptor. • Briefly explain the method of subtractive hybridization. • State why this method was so important in the characterization of the TCR.

30. What does it mean to say that TCRs belong to the Ig supergene family? • Briefly describe the heterodimeric structure of the TCR. • TCR genes use the same strategies as antibody genes to develop receptor diversity; however, TCR genes do not exhibit somatic hypermutation. Why? • The TCR is closely assoicated with another surface protein complex. What is its name and function?

31. Describe the three way complex that occurs during antigenic recognition by T cells. • T cells can react only with protein fragments. • What is this process called? • How does it occur? • Which pathway leads to antigen interaction with MHC-I molecules? • Which pathway leads to interaction with MHC-II molecules?

32. What are accessory molecules? • Give some examples. • Briefly discuss how they may be involved in antigen recognition by T cells.