INVOLVEMENT OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ANTIGENS IN T-CELL ACTIVATION

During the last few years ample evidence has been collected indicating a regulatory role for major histocompatibility complex class I antigens (Ag) in T cell activation. However, due to differential effects (stimulatory and inhibitory) of anti‐class I antibodies (Ab) observed under different conditions, no coherent scheme of the mechanism of action of these Ag has emerged. Here, we present evidence that the mode of action of anti‐class I Ab depends upon the presence or absence of monocytes/macrophages (MΦ) in the culture. The Ab inhibit Ag presentation by binding to MΦ. Coating of tetanus toxin ‐pulsed MΦ with anti‐class I Ab is sufficient to suppress T cell activation. On the contrary, these Ab enhance lectin‐ as well as phorbol ester‐induced T cell activation in the absence of MΦ. Cross‐linking of class I Ag on T cell surface mobilizes cytoplasmic Ca2+, and also enhances the CD3‐induced Ca2+ flux inside the cells indicating a functional relationship between CD3 and class I Ag. Though surface modulation and immunoprecipitation experiments do not indicate any physical association between these two types of molecules on the T cell surface, capping studies show that cross‐linking of class I Ag induces an association of these Ag with CD3. Binding of anti‐CD3 Ab enhances the strength of association between CD3 and class I Ag, and the former co‐caps completely with the latter. Based on these observations we propose that during antigen presentation MΦ (or Ag‐presenting cells) and T cells, besides interacting via peptide–class II Ag/CD3–T cell receptor complex formation, also interact through class I Ag. The latter interaction may stabilize the contact formation between T cells and Ag‐presenting cell and support T cell activation. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim