Lecture-7 Antigen process and presentation.pptx

To appraise the DC cytosol processing of an antigen and presentation by either MHC Class I or II transmembrane proteins to the effector cells.

1. Lecture-7 ANTIGEN PROCESSING AND PRESENTATION Prof. Sreerama Krupanidhi Email: [email protected]

2. Purpose To understand the DC cytosol processing of an antigen and presentation by either MHC Class I or II transmembrane proteins to the effector cells. 30-08-2024 Prof. Sreerama Krupanidhi 2

3. Expected Outcomes Development of MHC class I coupling with viral antigenic peptide will be known. Development of MHC class II coupling with bacterial antigenic peptide will be known. Antigen presentation ultimately eliciting immune response will be understood. 30-08-2024 Prof. Sreerama Krupanidhi 3

4. Antigen Processing and Presentation (PART II)_ MHC II Antigen Presentation Pathway (FL-Immuno_26).mp4 30-08-2024 Prof. Sreerama Krupanidhi 4

5. Antigen presentation is a Function of MHC Recognition of antigen coupled with MHC by T cells is necessary for induction of the immune response. 30-08-2024 Prof. Sreerama Krupanidhi 5 HLA class II. antigen TCR CD4 T lymfocyte APC lysozom ER, Golgi

6. Class I MHC pathway - processing endogenous cytosolic protein antigens Cytoplasmic peptides are actively transported into the ER; class I MHC molecules are available to bind peptides in the ER

7. Class I MHC pathway - processing of endogenous cytosolic protein antigens

8. Class I MHC pathway - processing of endogenous cytosolic protein antigens

9. Cytoplasmic peptides are actively transported into the ER; class I MHC molecules are available to bind peptides in the ER Class I MHC pathway - processing of endogenous cytosolic protein antigens

10. Cytoplasmic peptides are actively transported into the ER; class I MHC molecules are available to bind peptides in the ER Class I MHC pathway - processing of endogenous cytosolic protein antigens

11. Assembly and stabilization of class I MHC molecules • Newly formed class I chains associate with calnexin , a molecular chaperone, in the ER membrane. p> niicroglobulin + Peptides I.xit Rl.K Class I MHC Calnexin < a lnexi n-ass< iciated Calreticulin-tapasin C ass I MHC class 1 MHC a chain associated class I a chain molecule MHC molecule tapasin Calreticulin I apasin Calreticulin (. alnexin

12. Assembly and stabilization of class I MHC molecules. • Newly formed class I chains associate with calnexin , a molecular chaperone, in the ER membrane. p> niicroglobulin + Peptides I.xit Rl.K Class I MHC Calnexin Calreticulin-tapasin C ass I MHC associated class I a chain molecule MHC molecule tapasin Calreticulin I apasin Calreticulin (. alnexin Class I supported by Calnexin

13. Assembly and stabilization of class I MHC molecules. • Subsequent binding to B2-microglobulin releases calnexin and allows binding to the chaperonin calreticulin and to tapasin , which is associated with the peptide transporter TAP. + Peptides I.xit Rl.K Class I MHC Calnexin Calreticulin-tapasin C ass I MHC associated class I a chain molecule MHC molecule tapasin Calreticulin I apasin Calreticulin (. alnexin Class I supported by Calnexin Beta2 niicroglobulin

14. Assembly and stabilization of class I MHC molecules. • This association promotes binding of an antigenic peptide, stabilizes the class I molecule-peptide complex, allowing its release from the ER. p> niicroglobulin + Peptides I.xit Rl.K Class I MHC Calnexin Calreticulin-tapasin C ass I MHC associated class I a chain molecule MHC molecule tapasin Calreticulin I apasin Calreticulin (. alnexin Class I supported by Calnexin

15. Assembly and stabilization of class I MHC molecules . • Newly formed class I chains associate with calnexin , a molecular chaperone, in the ER membrane. • Subsequent binding to B2-microglobulin releases calnexin and allows binding to the chaperonin calreticulin and to tapasin , which is associated with the peptide transporter TAP. • This association promotes binding of an antigenic peptide, which stabilizes the class I molecule-peptide complex, allowing its release from the ER B 2 niicroglobulin + Peptides Class I MHC Calnexin Calreticulin-tapasin C ass I MHC associated class I a chain molecule MHC molecule tapasin Calreticulin I apasin Calreticulin (. alnexin Class I supported by Calnexin Exit from ER: presenting to CD8 cell

16. Assembly of class II MHC molecules

17. Assembly of class II MHC molecules

18. Assembly of class II MHC molecules • The bound invariant chain prevents premature binding of peptides to the class II molecule.

19. Assembly of class II MHC molecules • Digestion of the invariant chain leaves CLIP, a small fragment remaining in the binding groove of the class II MHC molecule.

20. Assembly of class II MHC molecules • HLA-DM, mediates exchange of antigenic peptides for CLIP ( Class II-associated invariant chain peptide ) .

21. 30-08-2024 Prof. Sreerama Krupanidhi 21 Dendritic cell priming T-cell

22. Summary - antigen presentation pathways 30-08-2024 Prof. Sreerama Krupanidhi 22 CD4 T lymfocyte B lymfocyte HLA class I. antigen TCR CD8 T lymfocyte APC ER, Golgi HLA class II. antigen TCR CD4 T lymfocyte APC lysozome ER, Golgi HLA class II. antigen TCR endogenous exogenous B lym ph cytes cell destruction immune response antibody production

23. Summary - antigen presentation pathways 30-08-2024 Prof. Sreerama Krupanidhi 23 CD4 T lymfocyte B lymfocyte HLA class I. antigen TCR CD8 T lymfocyte APC ER, Golgi HLA class II. antigen TCR CD4 T lymfocyte APC lysozome ER, Golgi HLA class II. antigen TCR endogenous exogenous B lym ph cytes cell destruction immune response antibody production

24. Summary - antigen presentation pathways 30-08-2024 Prof. Sreerama Krupanidhi 24 CD4 T lymfocyte B lymfocyte HLA class I. antigen TCR CD8 T lymfocyte APC ER, Golgi HLA class II. antigen TCR CD4 T lymfocyte APC lysozome ER, Golgi HLA class II. antigen TCR endogenous exogenous B lym pho cytes cell destruction immune response antibody production

25. Summary Antigen presentation is a function of MHC . Class I MHC pathway processes endogenous cytosolic protein antigens. Assembly and stabilization of class I MHC molecule are made with calnexin and tapasin chaperone molecules. Assembly and stabilization of class II MHC molecules are made with invariant chain and CLIP Class II MHC activates Th cell for the exogenous antigen neutralization. 30-08-2024 Prof. Sreerama Krupanidhi 25

26. Study Questions Explain class I MHC pathway of processing endogenous cytosolic protein antigens. Describe assembly and stabilization of class I MHC molecules. Elaborate on the assembly of class II MHC molecules to process antigen. Show a labelled display of antigen presentation pathways. How Does the principle of antigen presentation pave the way for designing vaccine? 30-08-2024 Prof. Sreerama Krupanidhi 26

27. Acknowledgements 8/30/2024 27 We acknowledge the online resources and public domains for the Preparation of the content to develop teaching material and for the dissemination of knowledge. Prof. Sreerama Krupanidhi

28. Thank you 30-08-2024 Prof. Sreerama Krupanidhi 28