Abstract
Many T cell responses are dominated by restricted TCR expression and can range from repeated usage of particular TCR Vβ-and/or Vα-elements, to the preferential usage of both V- and J-elements, often in conjunction with conserved V-D-J or V-J junctional sequences. Cytotoxic T lymphocytes specific for a K(b)-restricted determinant from the herpes simplex virus glycoprotein B (gB) preferentially express a dominant TCRBV10 β-chain with sequence conservation of a tryptophan-glycine located in the V-D junction. Here we have examined whether immunisation of C57BL/6 mice with the gB-peptide can mimic the CTL response seen after HSV1 infection. Immunisation with the gB- peptide resulted in the generation of gB-specific CTL that showed a similar TCRBV10 bias to that observed after HSV-1 infection. When the gB-determinant was expressed as a part of a fusion protein, immunised mice again exhibited the TCRBV10 bias with the junctional sequence conservation in the responding CTL. C57BL/6 mice were then immunised with variants of the gB-peptide that contained amino acid substitutions at positions previously predicted to contact the TCR β-chain CDR3. Analysis of the TCRBV usage of variant specific CTL lines showed that substitutions at the TCR-contact positions 4, 6 and 7 of the gB-peptide resulted in a loss of the TCRBV10 bias. These results suggest that the TCRBV10 bias seen in gB-specific CTL after HSV-1 infection is due to antigenic selection by the minimal peptide and is determined by residues proposed to contact the TCR β-chain CDR3.
| Original language | English |
|---|---|
| Pages (from-to) | 307-316 |
| Number of pages | 10 |
| Journal | Molecular Immunology |
| Volume | 35 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1 Apr 1998 |
| Externally published | Yes |
Keywords
- Glycoprotein B
- Herpes simplex virus
- T cell receptor
- V-region bias
Cite this
}
A dominant Vβ bias in the CTL response after HSV-1 infection is determined by peptide residues predicted to also interact with the TCR β- chain CDR3. / Turner, Stephen J.; Carbone, Francis R.
In: Molecular Immunology, Vol. 35, No. 5, 01.04.1998, p. 307-316.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - A dominant Vβ bias in the CTL response after HSV-1 infection is determined by peptide residues predicted to also interact with the TCR β- chain CDR3
AU - Turner, Stephen J.
AU - Carbone, Francis R.
PY - 1998/4/1
Y1 - 1998/4/1
N2 - Many T cell responses are dominated by restricted TCR expression and can range from repeated usage of particular TCR Vβ-and/or Vα-elements, to the preferential usage of both V- and J-elements, often in conjunction with conserved V-D-J or V-J junctional sequences. Cytotoxic T lymphocytes specific for a K(b)-restricted determinant from the herpes simplex virus glycoprotein B (gB) preferentially express a dominant TCRBV10 β-chain with sequence conservation of a tryptophan-glycine located in the V-D junction. Here we have examined whether immunisation of C57BL/6 mice with the gB-peptide can mimic the CTL response seen after HSV1 infection. Immunisation with the gB- peptide resulted in the generation of gB-specific CTL that showed a similar TCRBV10 bias to that observed after HSV-1 infection. When the gB-determinant was expressed as a part of a fusion protein, immunised mice again exhibited the TCRBV10 bias with the junctional sequence conservation in the responding CTL. C57BL/6 mice were then immunised with variants of the gB-peptide that contained amino acid substitutions at positions previously predicted to contact the TCR β-chain CDR3. Analysis of the TCRBV usage of variant specific CTL lines showed that substitutions at the TCR-contact positions 4, 6 and 7 of the gB-peptide resulted in a loss of the TCRBV10 bias. These results suggest that the TCRBV10 bias seen in gB-specific CTL after HSV-1 infection is due to antigenic selection by the minimal peptide and is determined by residues proposed to contact the TCR β-chain CDR3.
AB - Many T cell responses are dominated by restricted TCR expression and can range from repeated usage of particular TCR Vβ-and/or Vα-elements, to the preferential usage of both V- and J-elements, often in conjunction with conserved V-D-J or V-J junctional sequences. Cytotoxic T lymphocytes specific for a K(b)-restricted determinant from the herpes simplex virus glycoprotein B (gB) preferentially express a dominant TCRBV10 β-chain with sequence conservation of a tryptophan-glycine located in the V-D junction. Here we have examined whether immunisation of C57BL/6 mice with the gB-peptide can mimic the CTL response seen after HSV1 infection. Immunisation with the gB- peptide resulted in the generation of gB-specific CTL that showed a similar TCRBV10 bias to that observed after HSV-1 infection. When the gB-determinant was expressed as a part of a fusion protein, immunised mice again exhibited the TCRBV10 bias with the junctional sequence conservation in the responding CTL. C57BL/6 mice were then immunised with variants of the gB-peptide that contained amino acid substitutions at positions previously predicted to contact the TCR β-chain CDR3. Analysis of the TCRBV usage of variant specific CTL lines showed that substitutions at the TCR-contact positions 4, 6 and 7 of the gB-peptide resulted in a loss of the TCRBV10 bias. These results suggest that the TCRBV10 bias seen in gB-specific CTL after HSV-1 infection is due to antigenic selection by the minimal peptide and is determined by residues proposed to contact the TCR β-chain CDR3.
KW - Glycoprotein B
KW - Herpes simplex virus
KW - T cell receptor
KW - V-region bias
UR - http://www.scopus.com/inward/record.url?scp=0031842156&partnerID=8YFLogxK
U2 - 10.1016/S0161-5890(98)00051-0
DO - 10.1016/S0161-5890(98)00051-0
M3 - Article
VL - 35
SP - 307
EP - 316
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 5
ER -