1 / 16

The Structure and Function of Large Molecular Assemblies 38 th Crystallographic meeting, Erice

The Structure and Function of Large Molecular Assemblies 38 th Crystallographic meeting, Erice June 2006 TcR recognition of super-bulged viral epitopes Jamie Rossjohn. The Dept. of Biochemistry & Molecular Biology. Anti-viral immunity and the Killer T-cell.

risa-yang
Download Presentation

The Structure and Function of Large Molecular Assemblies 38 th Crystallographic meeting, Erice

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. The Structure and Function of Large Molecular Assemblies 38th Crystallographic meeting, Erice June 2006 TcR recognition of super-bulged viral epitopes Jamie Rossjohn The Dept. of Biochemistry & Molecular Biology

  2. Anti-viral immunity and the Killer T-cell

  3. MHC genes are highly polymorphic classical MHC-class I Potential TcR contact points Polymorphisms are concentrated in the cleft Alleles differ by single residues or up to 30 residues TcR 4 MHC 7 MHC anchor residues

  4. A forest of MHC peptide complexes

  5. - ++ +++ +++ +++ - + ++ + + + + CTL response and HLA-binding properties 13-mer LPEPLPQGQLTAY B35 motif * P** * * * * * * ** Y P2 P B*3501 B*3508 CTL response CTL response binding binding 13-mer 11-mer 9-mer B*3501 156 Leu B*3508 156 Arg

  6. Prominent Landscapes Highly mobile peptide HLA B*3508-13mer Super-bulged peptides can display differing degrees of mobility Varied prominent features

  7. TcR recognition of the B*3508/13-mer focuses on a bulged region of the peptide Eat as much as you want?

  8. TcR recognition of a super-bulged peptide Do such epitopes act as an obstacle for TCR ligation? Does the TcR deform the peptide upon ligation? Aim: Establish the structural basis of TcR recognition of super-bulged epitopes Hypothesis: This structural investigation will provide insights into MHC-restriction

  9. TcR recognition of a super-bulged viral peptide a1-helix

  10. A minimal footprint CDR2a Limited MHC contacts Orthogonal docking MHC-mediated contacts Typical footprint

  11. Alternative docking modes Twice as many peptide-mediated contacts compared to MHC-contacts Rocking atop the rigid epitope

  12. A restricted response, yet alloreactive B*3508 Kd = 9.9 mM B*3501 Kd = 35.1 mM B*3508 Cannot “see” B*3501 Cross-reacts onto B*4402 Restriction triad B*3501

  13. Conclusions • Long viral peptides in MHC-I immunity • Structural basis of recognition of super-bulged viral peptides • MHC-restriction

More Related