Analysis of the repertoire of cattle CD4(+) T cells reactive with bovine viral diarrhoea virus.
Cell-mediated immunity and CD4(+) cells in particular are important for the resolution of acute infection with non-cytopathic bovine viral diarrhoea virus (BVDV). CD4(+) T cells were shown to recognise virus-infected and non-infectious-protein-pulsed APCs, whereas CD8(+) T cells recognised only virus-infected APCs. T cell recognition was strain cross-reactive and MHC-restricted. Using native and recombinant antigens, we identified the structural glycoprotein E2 and the non-structural protein NS3 as dominant CD4(+) T cell determinants. The repertoire of CD4(+) T cell responses to E2 and NS3 was examined using inbred, homozygous cattle and overlapping synthetic peptides. The repertoire was biased toward conserved regions of NS3 and excluded the hypervariable regions of E2. The number of peptides that were recognised varied between animals but patterns could be distinguished in those animals that shared the same DRB3(*) allele. Of particular interest were: (i) a determinant that was recognised in the context of both DRB3(*) alleles (i.e. DRB3(*)2002 and DRB3(*)0701), (ii) two determinants that were juxtaposed to B cell sites, and (iii) a determinant that had structural analogy with a NS3 epitope previously described for the closely related hepatitis C virus. The minimum stimulatory sequence of the latter, NS3(397-414), was located to residues NS3(400-410).
Collen
T
T
Division of Immunology and Pathology, Institute for Animal Health, Compton, Berkshire RG20 7NN, UK. trevor.collen@bbsrc.ac.uk
Carr
V
V
Parsons
K
K
Charleston
B
B
Morrison
W I
WI
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D001908:Diarrhea Viruses, Bovine Viral / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010447:Peptide Hydrolases; D020365:RNA Helicases; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000956:Antigens, Viral; D010446:Peptide Fragments; D010447:Peptide Hydrolases; D020365:RNA Helicases; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C076551:gp53, bovine viral diarrhea virus; C086730:p80 protein, bovine viral diarrhea virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases