期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1990
卷号：87
期号：22
页码：9015-9019
DOI：10.1073/pnas.87.22.9015
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cytotoxic T lymphocytes (CTLs) have been shown to be relatively resistant to cytolytic attack by other CTLs. We show here, however, that cloned CTLs, in the absence of other cells, are destroyed by exposure to their cognate peptides (defined as those that in association with major histocompatibility complex proteins are recognized by the antigen-specific receptor of the T cell). Destruction is proportional to peptide concentration and can be prevented by a second peptide that competes with the cognate peptide for presentation by the class I major histocompatibility complex proteins of the CTLs. The speed and extent of peptide-induced changes in the appearance of CTLs suggest that the destruction may be due primarily to self-recognition and self-destruction of individual CTLs (suicide) rather than to the destruction of some CTLs by others of the same clone in the same culture (fratricide). This effect may also take place in vivo because the appropriately timed injection of a cognate peptide into ovalbumin-immunized mice appeared to deplete their spleens of primed anti-ovalbumin CTLs. The results point to a possible physiologic mechanism for postthymic elimination of cytolytic T cells that recognize their own peptides in association with their own major histocompatibility complex protein. The results also raise the possibility that cognate peptides might eventually prove therapeutically useful for eliminating CTL clones that cause pathological cell destruction, as in some autoimmune diseases and some viral infections.
