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 alphabeta 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 alphabeta 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 alphabeta, 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.
Silvestri
B
B
Department of Oncology and Surgical Sciences, Interuniversity Centre for Research on Cancer, University of Padova, Italy.
Calderazzo
F
F
Coppola
V
V
Rosato
A
A
Iacobelli
S
S
Natoli
C
C
Ullrich
A
A
Sures
I
I
Azam
M
M
Brakebush
C
C
Chieco-Bianchi
L
L
Amadori
A
A
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000378:metabolism*; D018956:CD5 Antigens / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D037502:Galectin 3; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D051379:Mice; D008970:Molecular Weight; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D018956:CD5 Antigens; D037502:Galectin 3; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002118:Calcium