A TUMOR ESCAPE VARIANT THAT HAS LOST ONE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I RESTRICTION ELEMENT INDUCES SPECIFIC CD8+ T-CELLS TO AN ANTIGEN THAT NO LONGER SERVES AS A TARGET

After loss of expression of a major histocompatibility complex class I K(k) allele, the escape variant of an immunogenic tumor grows progressively in normal mice. This progressor variant is resistant to killing by cytotoxic T lymphocytes (CTLs) directed against the A and B antigens presented by K(k). Although the variant retains the expression of the D(k) allele and is sensitive to CTLs directed against the C antigen presented by D(k), the variant failed to induce CTLs to this antigen in vivo. Instead, the variant induced CD8+ T cells directed to the A antigen. This was shown at the molecular level by T cell receptor beta chain sequence analysis of the responding cells. Further evidence for the presence of A antigen in the variant came from the finding that spleen cells of mice injected intraperitoneally with the variant tumor cells were primed for an anti-A CD8+ CTL response in vivo. Thus, in contrast to other variants that lost a target antigen and induced a CTL response to remaining target antigens, the K(k) loss variant continued to induce an immune response to a tumor antigen that is no longer presented on the tumor cell surface. Even though the variant escapes in a single step because an effective CTL response to secondary antigens is prevented, these secondary antigens remain as potential targets of immunotherapy on the variant's cell surface.