PDBsum entry 4p2o

Immune system

PDB id: 4p2o

Contents

Protein chains

175 a.a.

176 a.a.

200 a.a.

244 a.a.

20 a.a.

Ligands

NAG-FUC-NAG-FUC

NAG ×3

Waters ×118

References listed in PDB file

Key reference

• Title: Deconstructing the peptide-Mhc specificity of t cell recognition.
• Authors: M.E.Birnbaum, J.L.Mendoza, D.K.Sethi, S.Dong, J.Glanville, J.Dobbins, E.Ozkan, M.M.Davis, K.W.Wucherpfennig, K.C.Garcia.
• Ref.: Cell, 2014, 157, 1073-1087. [DOI no: 10.1016/j.cell.2014.03.047]
• PubMed id: 24855945

Note: In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above have been manually determined.

Abstract

In order to survey a universe of major histocompatibility complex (MHC)-presented peptide antigens whose numbers greatly exceed the diversity of the T cell repertoire, T cell receptors (TCRs) are thought to be cross-reactive. However, the nature and extent of TCR cross-reactivity has not been conclusively measured experimentally. We developed a system to identify MHC-presented peptide ligands by combining TCR selection of highly diverse yeast-displayed peptide-MHC libraries with deep sequencing. Although we identified hundreds of peptides reactive with each of five different mouse and human TCRs, the selected peptides possessed TCR recognition motifs that bore a close resemblance to their known antigens. This structural conservation of the TCR interaction surface allowed us to exploit deep-sequencing information to computationally identify activating microbial and self-ligands for human autoimmune TCRs. The mechanistic basis of TCR cross-reactivity described here enables effective surveillance of diverse self and foreign antigens without necessitating degenerate recognition of nonhomologous peptides.