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Structure of an autoimmune T cell receptor complexed with class II peptide-MHC : Insights into MHC bias and antigen specificity

Maynard, Jennifer; Lindkvist, Karin LU ; Wilson, Dianne H.; Adams, Erin J.; Blondelle, Sylvie E; Boulanger, Marty J.; Wilson, Darcy B. and Garcia, K. Christopher (2005) In Immunity 22(1). p.81-92
Abstract

T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class II MHC I-Au, recognition of the MHC is dominated by the Vβ domain of the TCR, which interacts with the MHC α chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly... (More)

T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class II MHC I-Au, recognition of the MHC is dominated by the Vβ domain of the TCR, which interacts with the MHC α chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly prefers the native MBP contact residues. We suggest that while TCR scanning of pMHC may be degenerate due to the TCR germline bias for MHC, recognition of structurally distinct agonist peptides is not indicative of TCR promiscuity, but rather highly specific alternative solutions to TCR engagement.

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author
publishing date
type
Contribution to journal
publication status
published
in
Immunity
volume
22
issue
1
pages
12 pages
publisher
Cell Press
external identifiers
  • scopus:12444298109
ISSN
1074-7613
DOI
10.1016/j.immuni.2004.11.015
language
English
LU publication?
no
id
691cdd3e-daed-46ee-85c9-6dff28fd7c87
date added to LUP
2017-02-15 15:34:23
date last changed
2017-10-29 04:57:57
@article{691cdd3e-daed-46ee-85c9-6dff28fd7c87,
  abstract     = {<p>T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class II MHC I-A<sup>u</sup>, recognition of the MHC is dominated by the Vβ domain of the TCR, which interacts with the MHC α chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly prefers the native MBP contact residues. We suggest that while TCR scanning of pMHC may be degenerate due to the TCR germline bias for MHC, recognition of structurally distinct agonist peptides is not indicative of TCR promiscuity, but rather highly specific alternative solutions to TCR engagement.</p>},
  author       = {Maynard, Jennifer and Lindkvist, Karin and Wilson, Dianne H. and Adams, Erin J. and Blondelle, Sylvie E and Boulanger, Marty J. and Wilson, Darcy B. and Garcia, K. Christopher},
  issn         = {1074-7613},
  language     = {eng},
  number       = {1},
  pages        = {81--92},
  publisher    = {Cell Press},
  series       = {Immunity},
  title        = {Structure of an autoimmune T cell receptor complexed with class II peptide-MHC : Insights into MHC bias and antigen specificity},
  url          = {http://dx.doi.org/10.1016/j.immuni.2004.11.015},
  volume       = {22},
  year         = {2005},
}