Role in T-cell activation for HLA class I molecules from accessory cells: further distinction between activation signals delivered to T cells via CD2 and CD3 molecules.
The immunological function of major histocompatibility complex molecules, including HLA class I molecules, is to present antigens and/or their processed peptides to various lymphocyte subpopulations. Thus, they play a pivotal role in regulatory interactions between cells of the immune system, which can result in the activation and function of T cells. We looked for a role of major histocompatibility complex molecules during T-cell activation induced by monoclonal antibody (mAb) or combinations of mAb recognizing the two well-characterized T-cell surface molecules CD3 and CD2. To activate T-cell peripheral blood lymphocytes, we used a CD3 mAb or two different pairs of CD2 mAb, CD2 "GT2 + T11(1)" and CD2 "D66 + T11(1)," which, as we have previously shown, deliver different signals of activation to T cells. Anti-HLA class I mAb blocked the activation induced by CD3 mAb or by CD2 GT2 + T11(1), but it did not block activation induced by CD2 D66 + T11(1). We observed this pattern of inhibition according to the stimulus used to activate T cells both when the anti-HLA class I mAbs were added to cultures of whole peripheral blood mononuclear cells and when they were fixed to monocytes only. In the latter case, purified monocytes were first incubated with the anti-HLA mAb (whether whole immunoglobulin or Fab fragment) and then fixed with paraformaldehyde before culture with autologous purified T cells. Anti-HLA class I fixed on monocytes prevented both interleukin 2 (IL-2) receptor expression and IL-2 synthesis on T cells. The inhibitory effects of anti-class I mAb bound to monocytes were not reversed by adding large amounts of recombinant IL-2 or recombinant IL-1, a finding consistent with the observations that accessory cells surface components can fully complement the signals directly delivered to T cells by CD2 or CD3 mAb. We conclude that HLA class I from accessory cells plays an important role in the early phase of T-cell activation when direct contacts between accessory cells and T cells are required.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D006680:HLA Antigens / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D011961:Receptors, Fc / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D006680:HLA Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins