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 Kk 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 Kk. Although the variant retains the expression of the Dk allele and is sensitive to CTLs directed against the C antigen presented by Dk, 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 Kk 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.
Seung
S
S
Department of Pathology, University of Chicago, Illinois 60637.
Urban
J L
JL
Schreiber
H
H
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001483:Base Sequence; D016827:CD8 Antigens / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006183:H-2 Antigens / Q000276:immunology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D016827:CD8 Antigens; D006183:H-2 Antigens; D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta