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PMID: 21490152 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structural basis of specificity and cross-reactivity in T cell receptors specific for cytochrome c-I-E(k).

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 186 ·No. 10 ·2011-05-15 ·Pages 5823-32

Newell EW, Ely LK, Kruse AC, Reay PA, Rodriguez SN, Lin AE, Kuhns MS, Garcia KC, Davis MM

Abstract

T cells specific for the cytochrome c Ag are widely used to investigate many aspects of TCR specificity and interactions with peptide-MHC, but structural information has long been elusive. In this study, we present structures for the well-studied 2B4 TCR, as well as a naturally occurring variant of the 5c.c7 TCR, 226, which is cross-reactive with more than half of possible substitutions at all three TCR-sensitive residues on the peptide Ag. These structures alone and in complex with peptide-MHC ligands allow us to reassess many prior mutagenesis results. In addition, the structure of 226 bound to one peptide variant, p5E, shows major changes in the CDR3 contacts compared with wild-type, yet the TCR V-region contacts with MHC are conserved. These and other data illustrate the ability of TCRs to accommodate large variations in CDR3 structure and peptide contacts within the constraints of highly conserved TCR-MHC interactions.

MeSH Terms
Animals Antigens, CD/chemistry,immunology,metabolism CD4-Positive T-Lymphocytes/immunology Complementarity Determining Regions/chemistry,immunology Cross Reactions Crystallography, X-Ray Cytochromes c/immunology,metabolism Humans Ligands Mice Models, Molecular Protein Binding Protein Structure, Tertiary Receptors, Antigen, T-Cell/chemistry,immunology,metabolism Receptors, Immunologic/chemistry,immunology,metabolism Recombinant Fusion Proteins/chemistry,immunology,metabolism Signaling Lymphocytic Activation Molecule Family Surface Plasmon Resonance
Chemicals
Antigens, CD Cd244a protein, mouse Complementarity Determining Regions Ligands Receptors, Antigen, T-Cell Receptors, Immunologic Recombinant Fusion Proteins Signaling Lymphocytic Activation Molecule Family Cytochromes c
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Newell Evan W
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
Ely Lauren K
Kruse Andrew C
Reay Philip A
Rodriguez Stephanie N
Lin Aaron E
Kuhns Michael S
Garcia K Christopher
Davis Mark M
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.1100197
Published
2011-05-15
Epub
2011-00-13
Pages
5823-32
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC3754796
Subset
IM
Grants
NIAID NIH HHS · U19 AI057229 · United States
NIAID NIH HHS · U19 AI090019 · United States
Howard Hughes Medical Institute · United States
Databases
PDB
3QIB, 3QIW, 3QJF, 3QJH
External Links
PubMed source DOI: 10.4049/jimmunol.1100197 PMC Full Text View journal details
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