A dominant V beta bias in the CTL response after HSV-1 infection is determined by peptide residues predicted to also interact with the TCR beta-chain CDR3.
Many T cell responses are dominated by restricted TCR expression and can range from repeated usage of particular TCR Vbeta- and/or Valpha-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 Kb-restricted determinant from the herpes simplex virus glycoprotein B (gB) preferentially express a dominant TCRBV10 beta-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 HSV-1 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 beta-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 beta-chain CDR3.
Turner
S J
SJ
Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria, Australia.
Carbone
F R
FR
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000737:chemistry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000096:biosynthesis / Q000737:chemistry; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D013945:Thymoma; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus