Cytotoxic Human HLA Class II Restricted Purified Protein Derivative-Reactive T-Lymphocyte Clones.

Abstract

Human T-lymphocyte clones specific for antigenic components of purified protein derivative (PPD) of tuberculin were generated by limiting dilution using in vitro PPD-activated peripheral blood mononuclear cells from a single donor. The HLA restriction specificity of eight clones that were cytotoxic against autologous PPD-pulsed monocyte targets, was examined against a panel of allogeneic PPD pulsed targets. In agreement with our findings with bulk-expanded PPD-reactive cytotoxic T lymphocytes, all clones were restricted by HLA class II antigens: seven by HLA-DR 2 and one by HLA-DRw10--the other HLA-DR antigen of the donor. All clones were CD3+, CD4+, CD8-. One clone exhibited, in addition to HLA-DR2 restriction, unrestricted cytotoxic alloreactivity against HLA-DR1. In monoclonal antibody-blocking experiments the latter clone was the only one that was blocked. Its lytic ability was abolished by two monoclonal antibodies against monomorphic HLA-DR determinants. The antigen specificity of the clones was studied by using autologous monocyte targets pulsed with antigens prepared from a range of different mycobacterial species. All seven HLA-DR2-restricted clones reacted with the majority of antigens tested. In contrast, the HLA-DRw10-restricted clone reacted exclusively with an antigen unique to PPD.