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 |
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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