Dissection of tumour-specific antigenicity.

Unique tumour-specific antigens have been detected on many tumours induced by physical or chemical carcinogens. Although a seemingly endless diversity of such antigens has been identified, very little is currently known about the nature and complexity of the antigenicity of any single tumour. We describe the characterization of the complex unique antigenicity expressed on an ultraviolet-light-induced tumour. Such tumours are highly immunogenic and are clearly subject to immunosurveillance in the normal host. The antigenicity of an ultraviolet-light-induced regressor tumour was dissected with the aid of monoclonal T-cell probes and with antigen-loss tumour variants that were selected in vitro or in vivo. It was demonstrated that the total antigenicity of this tumour consisted of multiple antigens, all of which were independent, tumour-specific and expressed simultaneously on the same tumour cell. Additional experiments determined which antigens were critical for tumour rejection by studying the in vivo growth behaviour of antigen-loss variants selected in vitro. Evaluation of the complexity of the host anti-tumour response revealed that a hierarchy existed in the host recognition of these antigens, a finding that should have important implications on the effectiveness of tumour rejection and immune escape. Finally, using tumour-specific monoclonal antibodies against the syngeneic tumour, investigation into the molecular nature of these tumour antigens indicated that some of these antigens represent novel class I major-histocompatibility-complex molecules. Thus we describe the complexity of a unique tumour-specific antigen and discuss the implications of this complexity on tumour immunity and tumour escape.