Differential effect on TCR:CD3 stimulation of a 90‐kD glycoprotein (gp90/Mac‐2BP), a member of the scavenger receptor cysteine‐rich domain protein family

We studied the effects of a 90‐kD glycoprotein (gp90/Mac‐2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non‐specific mitogens such as phytohaemagglutinin (PHA) and concanavalin A (Con A), but not pokeweed mitogen (PWM), was strongly reduced, probably due to the lectin‐binding properties of gp90/Mac‐2BP, the response to T cell receptor (TCR) agonists such as superantigens and allogeneic cells was potentiated. When lymphocytes were stimulated with different anti‐TCR:CD3 MoAbs, both in soluble and solid‐phase form, gp90/Mac‐2BP was able to down‐regulate the proliferative response to anti‐CD3 MoAb, whereas the response to anti‐TCR αβ MoAb was enhanced. A similar differential effect was observed when a MoAb against CD5 (another member of the scavenger receptor superfamily) was added to anti‐CD3 or anti‐TCR‐stimulated cells; anti‐CD5 MoAb strongly down‐modulated the CD3‐mediated response, whereas its presence in culture was associated with potentiation of the response to TCR αβ agonists. gp90/Mac‐2BP was able per se to up‐regulate Ca2+ levels in freshly isolated lymphocytes; moreover, its presence in culture was associated with increased Ca2+ mobilization following stimulation with anti‐TCR αβ, but not anti‐CD3 MoAb. These data indicate that gp90/Mac‐2BP could be able to influence some immune responses, possibly through multiple homologous interactions with other members of the scavenger receptor family; moreover, our findings suggest that signalling through the different components of the TCR:CD3 complex may follow distinct activation pathways into the cells.