International Immunology, Vol 9, 1319-1328, Copyright © 1997 by Oxford University Press
CM Jones, SC Cose and FR Carbone
TCR repertoire availability has the potential to influence the immune
response to foreign antigens. Here we have analysed how changes in V region
availability influence the H-2b-restricted cytotoxic T lymphocyte (CTL)
response to a dominant peptide determinant derived from the herpes simplex
virus glycoprotein B (gB). We have previously shown that C57BL/6 mice mount
a gB-specific, Kb-restricted CTL response which is dominated by a TCRBV10+
population and a TCRBV8S1+ subpopulation, both containing highly conserved
CDR3 elements. We find that this dominant gB-specific CTL pool is lost in
C57/L mice which have a different TCRBV haplotype. A population of CTL with
diverse TCRBV and junctional sequence usage, which otherwise represents a
minor subset in the gB-specific response, appears to emerge as a
consequence of this TCRBV gene variation. The loss of preferential V
region-encoded complementarity determining regions (CDR) 1- and/or
CDR2-ligand interactions in this emerging population also results in a
change in CDR3 sequence usage and a corresponding focusing of an otherwise
promiscuous pattern of cross-reactivity with a panel of gB498-505
substitution analogues. This suggests that the difference between the two
distinct TCR populations is the relative contributions of the CDR towards
ligand recognition. Therefore, preferential V region-ligand interaction, at
the expense of CDR3 peptide recognition, appears to control the dominant
TCR selection in the C57BL/6 response to this peptide determinant.
ARTICLES
Evidence for cooperation between TCR V region and junctional sequences in determining a dominant cytotoxic T lymphocyte response to herpes simplex virus glycoprotein B
Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria, Australia.
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