How a Single T Cell Receptor Recognizes Both Self and Foreign MHC

Leremy A. Colf, Alexander J. Bankovich, Nicole A. Hanick, Natalie A. Bowerman, Lindsay L. Jones, David M M. Kranz, K. Christopher Garcia

Research output: Contribution to journalArticle

Abstract

αβ T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 Å structure of the 2C TCR complexed with its foreign ligand H-2Ld-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2Kb-dEV8. 2C engages both shared and polymorphic residues on Ld and Kb, as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the Ld-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2Ld-QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3α interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalCell
Volume129
Issue number1
DOIs
StatePublished - Apr 6 2007

Fingerprint

T-Cell Antigen Receptor
Major Histocompatibility Complex
Ligands
Molecular Mimicry
Antigens
Peptides
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Colf, L. A., Bankovich, A. J., Hanick, N. A., Bowerman, N. A., Jones, L. L., Kranz, DM. M., & Garcia, K. C. (2007). How a Single T Cell Receptor Recognizes Both Self and Foreign MHC. Cell, 129(1), 135-146. https://doi.org/10.1016/j.cell.2007.01.048

How a Single T Cell Receptor Recognizes Both Self and Foreign MHC. / Colf, Leremy A.; Bankovich, Alexander J.; Hanick, Nicole A.; Bowerman, Natalie A.; Jones, Lindsay L.; Kranz, David M M.; Garcia, K. Christopher.

In: Cell, Vol. 129, No. 1, 06.04.2007, p. 135-146.

Research output: Contribution to journalArticle

Colf, LA, Bankovich, AJ, Hanick, NA, Bowerman, NA, Jones, LL, Kranz, DMM & Garcia, KC 2007, 'How a Single T Cell Receptor Recognizes Both Self and Foreign MHC', Cell, vol. 129, no. 1, pp. 135-146. https://doi.org/10.1016/j.cell.2007.01.048
Colf LA, Bankovich AJ, Hanick NA, Bowerman NA, Jones LL, Kranz DMM et al. How a Single T Cell Receptor Recognizes Both Self and Foreign MHC. Cell. 2007 Apr 6;129(1):135-146. https://doi.org/10.1016/j.cell.2007.01.048
Colf, Leremy A. ; Bankovich, Alexander J. ; Hanick, Nicole A. ; Bowerman, Natalie A. ; Jones, Lindsay L. ; Kranz, David M M. ; Garcia, K. Christopher. / How a Single T Cell Receptor Recognizes Both Self and Foreign MHC. In: Cell. 2007 ; Vol. 129, No. 1. pp. 135-146.
@article{5dc0a72862884557b7efbfce34e03691,
title = "How a Single T Cell Receptor Recognizes Both Self and Foreign MHC",
abstract = "αβ T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 {\AA} structure of the 2C TCR complexed with its foreign ligand H-2Ld-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2Kb-dEV8. 2C engages both shared and polymorphic residues on Ld and Kb, as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the Ld-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2Ld-QL9, the {"}wild-type{"} TCR-MHC binding orientation persists despite modified TCR-CDR3α interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.",
author = "Colf, {Leremy A.} and Bankovich, {Alexander J.} and Hanick, {Nicole A.} and Bowerman, {Natalie A.} and Jones, {Lindsay L.} and Kranz, {David M M.} and Garcia, {K. Christopher}",
year = "2007",
month = "4",
day = "6",
doi = "10.1016/j.cell.2007.01.048",
language = "English (US)",
volume = "129",
pages = "135--146",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - How a Single T Cell Receptor Recognizes Both Self and Foreign MHC

AU - Colf, Leremy A.

AU - Bankovich, Alexander J.

AU - Hanick, Nicole A.

AU - Bowerman, Natalie A.

AU - Jones, Lindsay L.

AU - Kranz, David M M.

AU - Garcia, K. Christopher

PY - 2007/4/6

Y1 - 2007/4/6

N2 - αβ T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 Å structure of the 2C TCR complexed with its foreign ligand H-2Ld-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2Kb-dEV8. 2C engages both shared and polymorphic residues on Ld and Kb, as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the Ld-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2Ld-QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3α interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.

AB - αβ T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 Å structure of the 2C TCR complexed with its foreign ligand H-2Ld-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2Kb-dEV8. 2C engages both shared and polymorphic residues on Ld and Kb, as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the Ld-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2Ld-QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3α interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.

UR - http://www.scopus.com/inward/record.url?scp=33947726614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947726614&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2007.01.048

DO - 10.1016/j.cell.2007.01.048

M3 - Article

C2 - 17418792

AN - SCOPUS:33947726614

VL - 129

SP - 135

EP - 146

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -