Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - SELFOR (How our adaptive immune system separates “self” from “foreign” – a physicochemical study of binding in cell contacts)

Teaser

The main goal of this project is to illuminate the problem of antigen discrimination by developing a physicochemical understanding of the interaction between T-cell receptors (TCRs) and peptide-loaded major histocompatibility complexes (pMHCs), and how this differs for pMHC...

Summary

The main goal of this project is to illuminate the problem of antigen discrimination by developing a physicochemical understanding of the interaction between T-cell receptors (TCRs) and peptide-loaded major histocompatibility complexes (pMHCs), and how this differs for pMHC with self and foreign peptides. The interaction between TCRs and pMHCs on contacting immune cells is the first, and arguably most important, step in initiating an adaptive immune response. It is also the interaction between TCR and pMHC that is the initial filter for our adaptive immune system to distinguish between our own cells and foreign pathogens, so called antigen discrimination. However, how this interaction differs between self and foreign pMHC, and how the binding kinetics is affected by TCR and pMHC being anchored to membranes, is missing. I will in SELFOR measure the binding kinetics between TCR in model cell membranes and pMHC on single cells, and how the binding varies between self and foreign pMHC. Parameters such as adhesion molecules, applied force on the bond, the co-receptor CD4 and TCR clustering are all crucial for proper T-cell signalling, but their influence on the TCR/pMHC binding kinetics is unknown, and will here be studied. The obtained data will finally be used to evaluate, and improve on, kinetic models of antigen discrimination. This altogether opens up for a fundamental understanding of binding between membrane-anchored molecules in general, and how this affects the TCR/pMHC interaction and antigen discrimination in particular.

Work performed

Reporting period 1:
* Recruitment of Mohammad Arif Kamal (postdoc), Tommy Dam (PhD student) and Manto Chouliara (PhD student).
* Development of a method to measure binding kinetics.
* Initial measurements on TCR/pMHC binding for self and foreign.
* Initial measurements on the influence of adhesion molecules on receptor/ligand binding.

Final results

\"WP1: To develop a general method to measure binding kinetics.

WP2: To characterize the interaction between TCR and pMHC.

WP3: To clarify how our adaptive immune system separates \"\"self\"\" from \"\"foreign\"\".\"

Website & more info

More info: http://www.physchem.lu.se/people/seniors/joensson/.