The T Cell Receptor Repertoire Influences VO Element Usage in Response to Myoglobin

نویسندگان

  • Garrison Fathman
  • Alexandra M. Livingstone
چکیده

T cell clones recognizing the sperm whale myoglobin (SpWMb) epitope 110-121 in association with H-2d major histocompatibility complex class II molecules display a very limited heterogeneity of T cell receptor (TCR) VO usage in DBA/2 mice. All clones previously tested used the same V(3 8.2 gene segment and very restricted junctional regions. To investigate the significance of this observation in vivo, we immunized DBA/2 mice with the intact SpWMb protein or peptide 110-121 . Only the V#8+ T cells showed any significant response to the 110121 epitope. The response to peptide 110-121 was then analyzed in mice which, either as a consequence of antibody depletion or through genetic deletion of TCR V0 genes, lacked V08+ peripheral T cells . DBA/2 mice depleted of V08+ T cells by antibody treatment responded poorly to the 110-121 peptide, and only at high antigen concentrations. In contrast, DBA/2Vf' mice (homozygous for a deletion ofmultiple VO gene segments including the V#8 family) made a response at least as great as that made by DBA/2 mice, even though the DBA/2V0°mice had a very restricted TCR Vii repertoire compared with DBA/2 mice. Mechanisms which might determine differences in the 110-121 specific response of DBA/2, DBA/2VO, and F23.1-treated DBA/2 mice are discussed .

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تاریخ انتشار 2003