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
| Autor: | Hans Schreiber, James L. Urban, Steven Seung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1993 |
| Předmět: |
Cytotoxicity
Immunologic CD8 Antigens Receptors Antigen T-Cell alpha-beta Immunology Molecular Sequence Data Immunodominance Major histocompatibility complex Lymphocyte Activation Mice Antigen Antigens Neoplasm T-Lymphocyte Subsets Immune Tolerance Immunology and Allergy Cytotoxic T cell Animals Gene Rearrangement beta-Chain T-Cell Antigen Receptor Mice Inbred C3H biology Base Sequence H-2 Antigens Articles Neoplasms Experimental Virology Molecular biology Tumor antigen CTL Tumor Escape Oligodeoxyribonucleotides biology.protein Female CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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