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 language | English (US) |
|---|---|
| Pages (from-to) | 135-146 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 129 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 6 2007 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
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 journal › Article
}
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.
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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 -