Involvement of major histocompatibility complex class I antigens in T cell activation

Abstract

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 (M phi) in the culture. The Ab inhibit Ag presentation by binding to M phi. Coating of tetanus toxin -pulsed M phi 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 M phi. 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 M phi (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.

Evidence for an Ongoing Role of Class I Histocompatibility Molecules for the Production of Interleukin‐2 in Response to Suboptimal Concentrations of Phytohaemagglutinin

“…We previously showed that dilutions of polyclonal anti-ZI^m similar to those used in the present study (1:50-1:100) actually induce significant lymphocyte activation, rather than inhibition, if phorbol esters are added to the cultures [13]. Many monoclonal antibodies to class I antigens will also activate T cells, but ihere is an additional requirement for a second cross-linking antibody before activation occurs [38,39], The precise mechanism of class I antigens in the activation ol'T cells remains unclear. Brams & Claesson [40] showed that mutant lines of thymoma cells thai had lost their class I histocompatibility expression failed to respond to anti-CD3 antibody with the production of IL-2.…”

The influence of curli, a MHC-I-binding bacterial surface structure, on macrophage–T cell interactions

“…Class I‐specific mAbs have been shown to be capable of inhibiting or promoting lymphocyte proliferation after cross‐linking surface MHC‐I [19–25]. Furthermore, CD3‐ or superantigen‐induced proliferation of T cells can be inhibited by cross‐linking MHC‐I with anti‐MHC‐I antibodies [20,24,26–28].…”

“…The MHC‐I‐transmitted signals are dependent on the CD3/TCR‐associated signal‐transducing machinery [19,21,22]. Furthermore, cross‐linking MHC‐I on the cell surface using MHC‐I‐specific antibodies has been shown to either inhibit or promote lymphocyte proliferation [19–25]. For example, cross‐linking MHC‐I on human peripheral CD3 + T cells using immobilized antibodies inhibited CD3‐ or superantigen‐induced proliferation of T cells [20,26,27].…”

Inactivation of human immunodeficiency virus (HIV)-1 envelope-specific CD8+ cytotoxic T lymphocytes by free antigenic peptide: a self-veto mechanism?

“…Sustained increases in intracellular Ca 2 § can often lead to unresponsiveness in CTL (46); consequendy, MHC class I modification of TCR-CD3 signals may represent another mechanism for the induction of anergy. T cell signaling through the class I molecule does not depend on the MHC cytoplasmic domain (47), but instead requires association of class I protein with other cell surface molecules (48,49). Most studies of MHC class I signal transduction and regulation of CTL effector function have involved the use of antibodies as an MHC cross-linking agent.…”