The role of different Invariant chain isoforms in MHCII trafficking and antigen presentation
Our group has since the early nineties aimed to understand the endocytic pathway and how peptide loading of the MHC class II complexes (MHC II) is regulated. A special focus for the group is to elucidate the contribution of the MHC II specific invariant chain (Ii) to the biogenesis of a specific endocytic pathway in antigen presenting cells (APCs). Ii plays a vital role in MHC II assembly and intracellular transport, but has been attributed an increasing number of additional functions in both in antigen presentation and cell signalling.
Our lab works in the junction of cell biology and immunology, and students attending our lab will be exposed to both fields. To understand immunology from a cell biological perspective is becoming increasingly important in order to develop new vaccine strategies and treatments towards various diseases.
Methods used in our lab:
DNA work (PCR with primer design and DNA cloning, QRT-PCR),
Cell work (Transfection, cell cloning, antigen presentaion assays, imaging by confocal microscopy of both live and fixed samples, lymphocyte isolation from blood)
Biochemistry (SDS-PAGE, Western blot)
Figure 1. Schematic illustration of Ii
Project:
There are four isoforms of Ii in humans, p33, p35, p41 and p43. Iip33 and Iip41 are distinguished by alternative splicing and these two isoforms yield two additional protein products due to an N-terminal cytoplasmic extension of 16 residues, which results from an alternative translation initiation site (figure 1)
Mice and humans are considered to have similar immune regulation, and results from mice experiments are often used to understand the human immune system. However, only the p33 (p31) and p41 isoforms are found in mice. Thus the two isoforms with the N-terminal extension are only found in humans and the exact role of these isoforms is still not clear.
In this project we want to investigate the role of the different isoforms of Ii, how they affect each other and how their expression level is regulated during an immune response. Development of vaccines and various treatments are always tested out in mice models prior to clinical trials in humans. It is therefore important to understand the contribution of the additional Ii isoforms in antigen presentation in order to translate treatment protocols from mice to humans.
Published Apr. 19, 2018 8:14 AM
- Last modified June 15, 2018 3:36 PM