1. Online Counseling Resource YCMOU ELearning Drive… School of Architecture, Science and Technology Yashwantrao Chavan Maharashtra Open University, Nashik – 422222, India 1

2. © 2008, YCMOU. All Rights Reserved.2 OC-SBT091-CP1-05 Introduction Programmes and Courses  SEP–SBT091–CP1-UN-01 2

3. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.3 Credits  Academic Inputs by Arun Punaji More. M.Sc. (Microbiology) ‏ Experience: 11 Years arunmesh@hotmail.com 3

4. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.4 How to Use This Resource  Counselor at each study center should use this presentation to deliver lecture of 40-60 minutes during Face-To-Face counseling.  Discussion about students difficulties or tutorial with assignments should follow the lecture for about 40-60 minutes.  Handouts (with 6 slides on each A4 size page) of this presentation should be provided to each student.  Each student should discuss on the discussion forum all the terms which could not be understood. This will improve his writing skills and enhance knowledge level about topics, which shall be immensely useful for end exam.  Appear several times, for all the Self-Tests, available for this course.  Student can use handouts for last minutes preparation just before end exam. 4

5. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.5 Learning Objectives  After studying this module, you should be able to: Describe the structure and functions of BCR Describe the structure and functions of TCR. 5

6. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.6 Introduction  Immune cells have got capability to interact with each other in mounting immune responses against infective agents.  The interactions between the immune cells for their activation involve the number of chemical mediators and surface receptors on the surfaces of immune cells.  It is interesting to know the structural similarity between the immunoglobulin molecules and the receptors present on the immune cells.  In this module students shall learn about the structures and functions of BCR and TCR. 6

7. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.7 B-Cells Receptors (BCR)-1  Structure of BCR:- B-Cell receptor is a transmembrane protein complex made of with membrane Ig molecule and disulfide linked heterodiamer called Ig- α/Ig-β. In BCR complex, membrane bound Ig molecule acts as ligand binding immunoglobulin molecule and Ig-α/Ig-β act as signal transducing molecule. The Ig-α and Ig-β polypeptide chains are long enough to transverse the cell membrane and interact with signalling molecules such as tyrosine kinase and G proteins in the cytoplasm. 7

8. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.8 B-Cells Receptors (BCR)-2  Structure of BCR:- The Ig-α polypeptide is made up of with 61 amino acids and Ig-β polypeptide chain is made up of with 48 amino acids. Cross linking of membrane bound Ig molecules produce stimulus in Ig-α/Ig-β heterodiamer which is transduced to intracellular signalling molecules such as tyrosine kinase and G proteins. Thus signalling from BCR is mainly mediated by tyrosine kinase. Tyrosine kinase get phosphorylated within intracellular chain of Ig-α/Ig-β. 8

9. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.9 B-Cells Receptors (BCR)-3  Structure of BCR:- The activated tyrosine kinase phosphorylate phospholipase C-γ (PLC-γ); the activated PLC-γ hydrolyzes membrane phospholipids liberating the potent second messenger proteins IP3 and DAG. The IP3 causes rise in intracellular Ca 2+ and DAG activate protein kinase C (PKC). Once this activation signal is transuded as a result of cross linking of BCR molecules as described above, active transcription factors are produced which travel into nucleus and stimulate or inhibit the transcription of specific genes. 9

10. School of Science and Technology, Online Counseling Resource… B-Cells Receptors (BCR)-4  Structure of BCR:- Membrane bound Ig and BCR molecules. © 2008, YCMOU. All Rights Reserved. 10

11. School of Science and Technology, Online Counseling Resource… B-Cells Receptors (BCR)-5  Structures of BCR, mIg, TCR and MHC molecules:- Comparison of structures of surface receptors molecules of immune cells. 11 © 2008, YCMOU. All Rights Reserved.

12. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.12 T-Cell receptors (TCR)  T-cell receptors are polypeptides present on T lymphocytes.  TCR is heterodimer protein molecule made up of with either α and β or γ and δ polypeptide chains; however the TCR with α and β chains predominates.  Structurally they resemble like Fab fragment of antibody molecules.  T-cell receptor forms a association with signal transducing protein complex called as CD3. 12

13. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.13 T-Cell receptors (TCR)-2  Unlike BCR proteins, TCR binds not only to antigen but also to class I and class II MHC proteins.  Thus TCR protein can recognize foreign antigens, native antigens and class I and class II MHC proteins.  TCR proteins show great diversity as immunoglobulins.  TCR show self-MHC restriction capability i.e. TCR recognizes antigen only when it is in association with MHC protein.  TCR with γ and δ chains do not show self- MHC restriction capability. 13

14. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.14 T-Cell receptors (TCR)-3  Structure of TCR:- T-cell receptor is made up of with either one α and β or with γ and δ chains. Each type of these T-Cell receptor chains has got two loops which are also called as domains. The structure of domains of α, β and γ, δ chains are similar to that of immunogobulins. The domains contain intrachain disulfide bonds. The domains at amino terminal show remarkable variations in its amino acid sequences and therefore also called as variable regions. 14

15. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.15 T-Cell receptors (TCR)-4  Structure of TCR:- The domains at carboxyl terminal show constant sequences of amino acids and therefore also called as constant regions. Each domain of this heterodimer possess one variable and one constant region. TCR molecule looks like Fab fragment of immunoglobulin. The α and β chains are connected to each other by a disulfide bond. Following this disulfide bond a small positively charged chains of 21 to 22 amino acids extends into plasma membrane from each chain; these chains interact with signal transducing CD3 proteins complex. 15

16. School of Science and Technology, Online Counseling Resource… T-Cell receptors (TCR)-5  Self-MHC restricting TCR receptor:- TCR is activated by foreign Antigen only when the antigen is Presented to TCR in association with MCH molecules; this is called as MCH self -restriction phenomenon. 16 © 2008, YCMOU. All Rights Reserved.

17. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.17 What We Learn…..  Structure and functions of BCR  Structure and functions of TCR 17

18. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.18 Critical Thinking Question  Why it was more difficult to study structure of TCR than that of BCR? 18

19. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.19 Hints For Critical Thinking Question  Difficulty in isolation of membrane bound TCR which are also insoluble.  TCR binds to not only antigen but also to MHC proteins. 19

20. School of Science and Technology, Online Counseling Resource… Study Tips  Book Title: Immunology Title: Immunology Author: Author: Richard A. Goldsby, Thomas Kindt, Barbara A. Osborne. Publication: Publication: W.H. Freeman and Company, New York. Book Title: Title: Microbiology Author: Author: Prescott, Harley and Klein's Publication: Publication: McGraw-Hill international edition. 20 © 2008, YCMOU. All Rights Reserved.

21. 21 End of the Presentation Thank You ! 21