The slides of Thomas Whalley (Cardiff University) at the CPP4 meeting on Sept 26th 2019 in Cambridge https://www.ccp4.ac.uk/wg/index.php

1. STACEI: STructural Analysis of TCR-
pEptide-MHC Interactions
Thomas Whalley
25/09/2019
http://github.com/whalleyt/stacei whalleyt@cardiff.ac.uk

2. What are TCR-pMHCs?
l Key part of the adaptive immune
system
l Essential for the clearance of
pathogens and cancer cells.
Malfunction can play a role in
autoimmunity
l Two main classes: MHC class I and
MHC class II restricted
peptide
TCRα
TCRβ
MHCα
MHCβ

3. Why do we need tools specifically for
TCR-pMHCs?
l Highly variable, need a methodology that can capture similarities
and differences in structures
l Essential for vaccine design, understanding cancer, autoimmunity,
immune function
l Growing pool of public structures
Attaf et al., 2015

4. STACEI pipeline

5. Contact analysis
l Calls made to CCP4 NCONT and output parsed
l Each contact categorised as van der Waals, hydrogen bond or
salt bridge
l Downstream visualisation in shiny R

6. Buried Surface Area
l Buried & available surface area, overall “availability”
l Used to find “pockets” in pMHC
l More visualisation in shiny R

7. Crossing angle calculation
x
yz
Crossing angle
(3D Rudolph Crossing angle)
x
yz
Rotation angle
(2D angle on the x,y plane)
θ
x
yz
Tilt angle
(2D angle on the z plane)
θθ

8. 3D visualisation
l Automate common visualisations ready for publication

9. Future work & conclusions
l Robust platform capable of handling multitude of data
l Extend Features of STACEI to make it easier to review
collections of structures
l Many applications of the annotated data
l Open to requests!

10. Acknowledgements
l Systems Immunity URI,
l Cardiff University
- Prof. Andrew Sewell
- Dr. Barbara Szomolay
- Dr. Pierre Rizkallah
l Biomedicine Discovery Institute,
l Monash University
- Dr. Bruce MacLachlan
l Immunocore Ltd.
- Dr. David Cole
http://github.com/whalleyt/stacei whalleyt@cardiff.ac.uk