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) belongin g to the scavenger receptor family, present in normal serum and at inc reased levels in inflammatory disease and cancer patients, on some T c ell function parameters. Whereas the lymphocyte proliferative response to non-specific mitogens such as phytohaemagglutinin (PHA) and concan avalin A (Con A), but not pokeweed mitogen (PWM), was strongly reduced , probably due to the lectin-binding properties of gp90/Mac-2BP, the r esponse to T cell receptor (TCR) agonists such as superantigens and al logeneic cells was potentiated. When lymphocytes were stimulated with different anti-TCR:CDS MoAbs, both in soluble and solid-phase form, gp 90/Mac-2BP was able to down-regulate the proliferative response to ant i-CD3 MoAb, whereas the response to anti-TCR alpha beta MoAb was enhan ced. A similar differential effect was observed when a MoAb against CD 5 (another member of the scavenger receptor superfamily) was added to anti-CD3 or anti-TCR-stimulated cells; anti-CDS MoAb strongly down-mod ulated the CD3-mediated response, whereas its presence in culture was associated with potentiation of the response to TCR alpha beta agonist s. 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 alpha beta, but not anti-CD3 MoAb. These data indicate that gp90/Mac-2 BP could be able to influence some immune responses, possibly through multiple homologous interactions with other members of the scavenger r eceptor family; moreover, our findings suggest that signalling through the different components of the TCR:CD3 complex may follow distinct a ctivation pathways into the cells.