Monoclonal antibodies to common epitopes of the human alpha/beta T-cell receptor preferentially activate CD45RA+ T-cells.
The murine monoclonal antibody BMA 031 (IgG2b) is directed to a monomorphic epitope on the human alpha/beta T-cell receptor. In contrast to anti-CD3 antibodies of the IgG2b isotype, BMA 031 is able to induce a proliferative response in T-cells from IgG2b low responders. This response occurs independently of cross-linking conditions indicating that the mode of activation differs from stimulation by the anti-CD3 antibody OKT3 (IgG2a) which strictly depends on cross-linking conditions. to further characterize the stimulatory potential of the two antibodies we studied the lymphocyte subsets responsive to stimulation by BMA 031 and OKT3. In CD45RA+ cells both antibodies exhibited similar effects. They induced weak expression of the 55-kDa chain of the interleukin-2 receptor (CD25), virtually no interleukin-2 secretion, but nevertheless strong proliferation. In CD45R0+ cells OKT3 and BMA 031 showed markedly different effects. OKT3 stimulated strong CD25 expression, strong interleukin-2 production, and marked proliferation. In contrast, CD45R0+ cells stimulated by BMA 031 showed only weak CD25 expression but neither interleukin-2 production nor proliferation. These data suggest that CD45RA+ and CD45R0+ cells differ in their capability to produce interleukin-2 upon stimulation via the CD3/T-cell receptor complex and also in the requirement for interleukin-2 to mount a proliferative response. The differential effect of OKT3 and BMA 031 in CD45R0+ cells probably results from the failure of BMA 031 to trigger interleukin-2 production which may be a consequence of its inability to induce CD3/T-cell receptor cross-linking in IgG2b low responders BMA 031 is therefore a useful tool for the selective activation of CD45RA+ cells in these individuals.
Schwinzer
R
R
Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Federal Republic of Germany.
Schlitt
H J
HJ
Wonigeit
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002455:Cell Division; D002460:Cell Line; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000276:immunology; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens