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A novel MHC class I molecule as a tumour-specific antigen. Correlation between the antibody-defined and the
Abstract:
Ultraviolet light (UV)-induced tumours in mice are often highly immunogenic and have unique (individually specific) antigens which cause tumour rejection in normal mice. The molecular nature of these unique 'rejection' or 'transplantation' antigens is not known. We have recently isolated a syngeneic monoclonal antibody (mAb), CP28, that recognizes a unique tumour-specific antigen on the UV-induced regressor tumour 1591-RE. Further analysis revealed that the antibody-recognized antigen represents a novel major histocompatibility complex (MHC) class I molecule. However, the relationship of this molecule to the unique T cell-recognized antigen that causes tumour rejection remained unresolved. In this study we have explored the relationship of the antibody-defined tumour-specific novel class I molecule to the rejection antigen, that we have previously defined with a cytolytic T cell (CTL) clone ('anti-A'). Two different lines of evidence suggested a close relationship. First, it was found that random subclones of the 1591-RE tumour expressed different levels of the CP28-defined antigen which correlated with the level of lysis by the anti-A CTL clone. Second, the selection of antigen-loss variants using either the anti-A CTL clone or the mAb CP28 resulted in the simultaneous loss of both the CP28 as well as the 'A' antigen. This tight correlation strongly suggests a relationship between the antibody-defined and the T cell-defined antigen. However, the role of the antibody-recognized antigen in causing transplantation rejection still needs to be determined.
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