TI  - Characterization of a novel high affinity human  <prot><prot>IL-7</prot> receptor</prot> . Expression
      on T cells and association with  <prot>IL-7</prot>  driven proliferation.
PG  - 4753-63
AB  - Although both unstimulated and activated human T cells express high
      affinity <prot>IL-7R</prot>, only activated T cells can proliferate to IL-7. This
      responsiveness may occur as a direct result of changes in the structure of
      the <prot>IL-7R</prot> during T-cell activation. We have previously demonstrated such
      changes by affinity cross-linking studies, and have shown that
      unstimulated human T cells express a single <prot>IL-7R</prot> of 90 kDa, whereas
      activated T cells express an additional 76-kDa <prot>IL-7</prot> binding protein. In
      this study the origin and function of the <prot>p90</prot> and <prot>p76</prot> molecules have been
      investigated. To determine the role of each of these receptors in <prot>IL-7</prot>
      driven proliferation, <prot>IL-7R</prot> expression and proliferative capacity were
      monitored during mitogenic stimulation. These analyses showed that the
      ability of PBMC to proliferate to <prot>IL-7</prot> correlated with expression of the
      <prot>p76</prot> <prot>IL-7R</prot>, and not with expression of the <prot>p90</prot> <prot>IL-7R</prot>. <prot>IL-7</prot>-driven
      proliferation is mediated via high affinity <prot>IL-7R</prot>, and accordingly,
      Scatchard analysis revealed that, like the <prot>p90</prot>  <prot>IL-7R</prot> , the  <prot>p76</prot> <prot>IL-7R</prot>  bound
        <prot>IL-7</prot>   with dual (high; Kd 38 pM and low; Kd 360 pM) affinity.
      Deglycosylation studies showed that the <prot>p90</prot> and <prot>p76</prot> <prot>IL-7R</prot> are not simply
      differently glycosylated isoforms of a single receptor. In agreement, mAb
      to the previously cloned <prot>IL-7R</prot> were found to stain unstimulated T cells
      that express only the <prot>p90</prot> <prot>IL-7R</prot> but not T-cell clones that express
      predominantly the <prot>p76</prot> <prot>IL-7R</prot>. These antibodies also immunoprecipitated the
      cloned <prot>IL-7R</prot> as a 90-kDa species from both 125-I-surface-labeled resting
      and activated T cells, but were unable to precipitate the 76-kDa <prot>IL-7R</prot>. In
      addition, PCR analysis of <prot>p76</prot>-expressing cells could not detect splicing
      of the extracellular domain of the cloned <prot>IL-7R</prot>, thereby excluding the
      possibility that the <prot>p76</prot> <prot>IL-7R</prot> is a previously undescribed splice variant
      of the cloned <prot>IL-7R</prot>. These data demonstrate that the <prot>p90</prot> <prot>IL-7R</prot> is the
      T-cell homologue of the cloned <prot>IL-7R</prot>, and imply that the <prot>p90</prot> and <prot>p76</prot> <prot>IL-7R</prot>
      have different extracellular domains. Taken together these data suggest
      that the 76-kDa receptor is a novel high affinity <prot>IL-7R</prot> that may be
      necessary for <prot>IL-7</prot> driven proliferation in human T cells.
AD  - Kennedy Institute of Rheumatology, London, United Kingdom.
