Identification and biochemical characterization of human plasma soluble IL-7R: lower concentrations in HIV-1-infected patients.
The IL-7R alpha-chain and the common gamma-chain (gamma(c)) are both components of IL-7R. Human plasma harbors soluble forms of IL-7R (sIL-7Ralpha and sgamma(c)) that are detected and assayed by Western blotting, showing that the levels of sIL-7Ralpha are higher than the levels of sgamma(c) (47.5 ng/ml and 1.5 ng/ml, respectively). Gel electrophoresis and tandem mass spectrometry used to analyze deglycosylated, affinity-purified protein showed that sIL-7Ralpha is generated through differentially spliced mRNA, not by membrane receptor shedding. Plasma sIL-7Ralpha and sgamma(c) are present as heterocomplexes and sgamma(c) was found to be mainly associated with sIL-7Ralpha. The affinities of two IL-7 binding sites (K(d) = 35 +/- 8 pM and K(d) = 3 +/- 1 nM) were similar to that of the membrane receptor, suggesting that the sIL-7Ralpha/sgamma(c) complex retains high affinity for IL-7. sIL-7Ralpha mRNA is constitutively present among peripheral T lymphocytes and is down-modulated in vitro by IL-7. Chronically HIV-1-infected patients (n = 20) showed no significant (p > 0.714) variation in sgamma(c) levels and a significant (p < 0.0014) 2-fold decrease in plasma sIL-7Ralpha levels compared with those in control healthy individuals. Plasma IL-7 and sIL-7Ralpha levels did not show any obvious relationship.
Rose
Thierry
T
Institut Pasteur, Unité d'Immunogénétique Cellulaire, Paris France.
Lambotte
Olivier
O
Pallier
Coralie
C
Delfraissy
Jean-François
JF
Colle
Jean-Hervé
JH
D000328:Adult; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D015658:HIV Infections / Q000097:blood* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013058:Mass Spectrometry; D008875:Middle Aged; D008969:Molecular Sequence Data; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012995:Solubility
D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D012333:RNA, Messenger