B Cell & T Cell Receptors.pptx

Immunity

1. B Cell & T Cell Antigen Specific Receptors

2. B cell Antigen Specific Receptor B-cell receptors (BCRs) are membrane-bound immunoglobulins that recognize and bind foreign proteins (antigens). BCRs are formed through  random somatic changes of germline DNA , creating a vast repertoire of unique sequences that enable individuals to recognize a diverse range of antigens.

3. What are the components of a BCR receptor ? Each cell-surface receptor has three main components:  A n external ligand-binding domain A hydrophobic membrane-spanning region A n intracellular domain inside the cell .

4. What activates the B cell receptor? B-cell activation is triggered by  the binding of ligand (referred to as antigen) to the B-cell receptor (BCR), which initiates a cascade of intracellular signaling leading to the internalization of antigen for processing and presentation to T cells .

5. Where is the B cell receptor (BCR) Located? The B cell receptor is transmembrane protein composed of a immunoglobulin molecule and a signal transduction moiety.

6. What is B cell receptor complex? The B-Cell Receptor complex usually consists of an antigen-binding subunit (the membrane immunoglobulin or MIg ), which is composed of two IgHs (Immunoglobulin Heavy Chains) and two IgLs (Immunoglobulin Light Chains) , and a signaling subunit which is a disulfide-linked heterodimer of Ig-Alpha ( CD79A) and Ig-Beta (CD79B)

7. What are the differences between B cell receptors and T cell receptors?                                   B cell receptor is a transmembrane receptor protein located on the outer surface of B cells.   T cell receptor is an antigen recognizing molecule present on the surface of T lymphocytes . B cell receptor recognizes unprocessed antigens . T cell receptor recognizes antigens displayed on MHC Class I and MHC Class II molecules on the surface of antigen presenting cells/accessary cells .

8. How do B cell receptors recognize antigens? B cells respond to antigens by engagement of their B-cell antigen receptor ( BCR ) and of co-receptors through which signals from helper T cells or pathogen-associated molecular patterns (PAP) are delivered.

9. Do B cells have MHC 1 or 2? Besides secreting antibodies, B cells express  MHC class II  and serve as antigen-presenting cells (APCs) for CD4 +   helper T cells .

10. What are antigen Presenting cells? Macrophages Dendritic cells B cells

11. How many binding sites does BCR have? Two Two heavy (H) chains and two light (L) chains are held together by inter-chain disulfide bonds , forming  two identical antigen-binding sites   .

12. What is required for B cell activation? Naïve B cell activation requires antigen recognition by the Ig receptor. The additional signals that can come either from a CD4 +   Helper T cell (thymus-dependent ) O r , in some cases, directly from microbial components (T independent ).

13. How does B cell activation begin? B cell activation is initiated  by the binding of antigen to the B cell receptor (BCR)  that triggers a number of signaling cascades that ultimately lead to B cell activation.

14. Do B cells bind to MHC? T cells bind antigens that have been digested and embedded in MHC molecules by APCs   B cells function as Antigen Presenting Cells (APC) that bind intact antigens that have not been processed .

15. How do B cells digest antigens? B Cells as Antigen-Presenting Cells Professional antigen-presenting cells (APCs) take up antigen through  phagocytosis , fluid-phase pinocytosis , or receptor-mediated endocytosis   for processing, loading of the digestion products onto MHC Class II (MHC II) and presentation to CD4 Helper T cells.

16. How many B cell receptors are there? 10 5 Each B cell has approximately 10 5  such receptors in its plasma membrane. E ach of these receptors is stably associated with a complex of transmembrane proteins that activate intracellular signaling pathways when antigen binds to the receptor .

17. Comparative Structure of BCR and TCR Receptor Complexes BCR complex is composed of surface immunoglobulin with two heavy chains and two light chains along with Ig-Alpha ( CD79A) and Ig-Beta (CD79B) TCR complex is composed of one alpha and one beta chains along with two units of CD3 molecules

18. T cell Receptor (TCR) Principal component TCR was a heterodimeric 90kDa protein composed of a 40kDa and a 50kDa molecule ( α and β chains) Surface molecule on T cells Recognize Ag presented in MHC context Similar to Immunoglobulin Two types of TCR α β : predominant in lymphoid tissues γ δ : enriched at mucosal surfaces

19. T cell antigen receptor: Some Fundamentals One T-cell has one type of TCR One T-cell has one TCR with a wholly unique specificity . One T-cell has as many as 100,000 identical TCR’s . There are two important types of T-cells: T H & T C .

20. Structure of the TCR ( αβ ) Regions Short cytoplasmic tail- cannot transduce activation signal Transmembrane with hydrophobic AAs Both α and β have a variable (V) and constant (C) region V region is hypervariable, determines Ag specificity

21. What Cell Receptors do? Two things: Respond to MHC Respond to Ag More exactly, they see one histotope and many, many types of processed antigens.

22. TCR

23. Structure of the TCR ( αβ ) Heterodimer α and β chains approx equal length

24. Important Aspects of TCR Each T cell has TCR of only ONE specificity Allelic exclusion αβ TCR recognizes Ag only in the context of cell-cell interaction and in correct MHC context γδ TCR recognizes Ag in MHC-independent manner Response to certain viral and bacterial Ag

25. Genetic basis for receptor generation Accomplished by recombination of V, D and J gene segments TCR β chain genes have V, D, and J TCR α chain genes have V and J

26. TCR and CD3 complex TCR is closely associated with CD3 complex Group of 5 proteins Commonly called “invariant” chains of TCR Role of CD3 complex CD3 necessary for cell surface expression of TCR transduces signal after Ag interaction with TCR

27. Key steps in T cell activation APC must process and present peptides to T cells T cells must receive co-stimulatory signal Accessory adhesion molecules stabilize binding of TCR and MHC Signal from cell surface is transmitted to nucleus Cytokines produced help drive cell proliferation

28. The T cell antigen receptor V a V b C a C b Carbohydrates Hinge Monovalent Resembles an Ig Fab fragment Fab V H V L Fc C L C H V L V H C H C L C H C H C H C H No alternative constant regions Transmembrane region Never secreted Domain structure: Ig gene superfamily Heterodimeric, chains are disuphide-bonded Cytoplasmic tail Very short intracytoplasmic tail + + + Positively charged amino acids in the TM region Antigen combining site Antigen combining site made of juxtaposed V a and V b regions 30,000 identical specificity TcR per cell

29.  T cells Distinct lineage of cells with unknown functions 1-5% of peripheral blood T cells In the gut and epidermis of mice, most T cells express  TcR Ligands of  TcR are unknown Possibly recognise: Antigens without involvement of MHC antigens - CD1 Class IB genes

30. Role of MHC in immune response TCR recognizes Ag presented in MHC Context is important Binding of Ag peptides in non-covalent Two types of MHC (class I and class II) are recognized by different subsets of T cells CTL recognizes Ag peptide in MHC class I T-helper recognizes Ag peptide in MHC class II

31. Structure of MHC class I Two polypeptide chains Long α chain and short β

32. Structure of MHC class I Four regions Cytoplasmic contains sites for phosphorylation and binding to cytoskeleton Transmembrane contains hydrophobic AAs Highly conserved α 3 domain binds CD8 Highly polymorphic peptide binding region formed by α 1 and α 2

33. Structure of MHC class II Two polypeptide chains α and β approx equal length

34. Structure of MHC class II Four regions Cytoplasmic contains sites for phosphorylation and binding to cytoskeleton Transmembrane contains hydrophobic AAs Highly conserved α 2 and β 2 domains binds CD4 Highly polymorphic peptide binding region formed by α 1 and β 1

35. Important aspects of MHC Individuals have a limited number of MHC alleles for each class High polymorphism in MHC for a species Alleles for MHC genes are co-dominant Each MHC gene product is expressed on surface of individual cell

36. Important aspects of MHC Each MHC has ONE peptide binding site But each MHC can bind many different peptides Only one at a time Peptide binding is “degenerate” MHC polymorphism is determined in germline NO recombination mechanisms for creating diversity in MHC Peptide must bind with individual’s MHC to induce immune response