Ubiquitination is a Post-translational modification that helps in many important cellular processes like antigen processing

1. Antigen Processing
Presented By: Aleena Haqqi

2. ANTIGEN PROCESSING &
UBIQUITINATION
Antigen processing
 Protein antigen is ingested by APC partially ingested into peptide fragments
and displayed on MHC-I &MHC-II
• MHC I - Endogenous Pathway - Ubiquitination & Proteasomes
• MHC II - Exogenous Pathway – Endosomes
(MHCII ubiquitination controls MHCII intracellular transport, its impact in
antigen presentation is not clearly established)
Ubiquitination
 Adding ubiquitin to lysin residue on substrate protein leading to formation of
polyubiquitinated substrate.

3. Process of Ubiquitination

4. Proteasome and
antigen processing:
1- Peptide associated with
class 1 are generated in
cytosol
2- Protease
3- Proteasome’s ability to
cleave preferentially after
hydrophobic or basic
residues, to generate
peptides in the range of
three to 22 residues with a
mean length of eight to
nine residue.
4-Peptides generate
translocated into ER.
5-Polyubiquitination
through Lysine48 (K48)
target substrate protein
for proteosomal
destruction By 26S
proteasome.
5-26S Proteasome are
important to cleave
proteins into peptides
and are loaded on
MHC-1 to produce
cytotoxic T cells.

5. 6- This proteasome eliminates most of foreign and
non functional proteins by degrading them into
short peptide.
7- Immunoproteasomes such as INF Gamma
enhances antigen presentation.
8- Correct length of peptide presented by MHC-1 .

6. MHC class 1 Antigen Processing

7. References
1) Strehl, B., Seifert, U., Kruger, E., Heink, S., Kuckelkorn, U., & Kloetzel, P.-M. (2005).
Interferon-gamma, the functional plasticity of the ubiquitin-proteasome system, and
MHC class I antigen processing. Immunological Reviews, 207(1), 19–30. doi:
10.1111/j.0105-2896.2005.00308.x
2) Oh, J., & Shin, J. S. (2015). Molecular mechanism and cellular function of MHCII
ubiquitination. Immunological reviews, 266(1), 134–144.
https://doi.org/10.1111/imr.12303
3) Pamer, E., & Cresswell, P. (1998). Mechanisms Of Mhc Class I–Restricted Antigen
Processing. Annual Review of Immunology, 16(1), 323–358. doi:
10.1146/annurev.immunol.16.1.32