Dr. Kathy McCoy kmccoy@vcu.edu

1. Dr. Kathy McCoykmccoy@vcu.edu

2. Antigen receptors Isotypes Precursor T cells acquire TCR expression in the thymus T cells do not change their TCR - No isotype switching

3. T Cell Receptors • Associate with other molecules: CD3 complex for both isotypes CD4 or CD8 for  TCR • Function is T cell activation • Specific & diverse

4.  T Cells • < 5% of peripheral T cells • Predominate in epithelium • Limited V gene usage in epithelium • Cytotoxic cells and secrete cytokines • Part of mucosal immunity and cell-mediated immunity • Referred to as innate-like

5. Antigen receptors Co-receptors Cytotoxic cells No preferential use of V or V genes

6. CD4+ T cell subsets loosely based on cytokines produced Classical Helper Cells 3 Subsets

7. Variable & Constant Regions

8. IgG vs. TCR

9. Complementarity Determining Regions CDR’s = Hypervariable Regions

10. * *

11. Important for T cell responses and T cell maturation in the thymus

12. or CD8

14. Required for cell surface expression & signal transduction CD3 Complex

15. Most diversity in CDR3 regions Flat Top CDR3 CDR3

16. V regions form a barrel Shorter, fatter, and more rigid than Ig Hinge

18. No Isotype Switching

20. Human No Isotype Switching

21. Mouse Organized into gene clusters - One cluster used per T cell clone

22. Recombination Signal Sequences

23. Recombination Signals: Heptamer- nonamer with 12 or 23 NA spacer 12/23 Rule Requires recombination activating genes: RAG-1 & RAG-2 Hairpin loop DNA circle deleted Inversion - less common

24. Second Increases probability of cell survival Also occurs in b and g loci

25. Generation of Diversity No Somatic Hypermutation - No Affinity Maturation

26. Allelic Exclusion

27. Allelic Exclusion • Not as strict as in B cells • Usually on a functional level, but not necessarily on a molecular level • Mature T cells can express 2 TCR’s using 3 chains • Productive  rearrangement inhibits additional  rearrangements •  chain stimulates  rearrangement •  rearrangement deletes  locus •  and  loci encode transcription silencers

28. TCR’s vs. Ig’s • TCR's do not isotype switch • TCR’s lack Fc portion & are not secreted • TCR’s for T cell activation & lack additional functions that Ig’s have • TCR's are monovalent • Similar gene rearrangement mechanisms, but TCR’s do not rearrange in B cells & visa versus • Main mechanisms for generation of diversity: Junctional • No somatic hypermutation or affinity maturation