Cognate Peptide-Induced Destruction of CD8⁺ Cytotoxic T Lymphocytes Is Due to Fratricide

The Journal of Immunology, July 15, 1993, vol. 15 #2, pp. 658-667

Michael W.-C. Su, Peter R. Walden, and Herman N. Eisen

In the absence of other cells, cloned CTL in culture can undergo massive destruction upon the addition of a peptide that is recognized, in association with the CTL’s class I MHC proteins, by the CTL’s Ag-specific ICR. To determine whether the destruction is a result of the individual CTL’s recognition via its own ICR of peptide-MHC-I complexes on its own surface ("suicide"), or to cytolytic attack by some CTL on others in the same culture ("fratricide"), we compared the rate of peptide-induced cell death in conventional cultures, where CTL are free to establish cell-cell contacts, with other cultures in which individual CTL were prevented from forming cell-cell contacts by encasing them individually in agarose gel microdrops. The differences were dramatic: in the presence of high concentrations of peptide (10 million fold greater than is necessary to support 500/n lysis of conventional target cells by these CTL) cell death was linear over 0 to 8 h in conventional cultures, at a rate of about l0% per hour, whereas in the presence of the same high concentration of peptide over the same time course, no death was detected among the cells encased in agarose gel microdroplets. The results demonstrate an absolute requirement for cell-cell contact in the destruction of cloned CIL in culture with their cognate peptides at high concentration. Using an increase of intracellular calcium ion concentration ([Ca²⁺]_i) as a measure of T-cell activation, we also found that peptide-dependent activation of CIL likewise depends upon cell-cell contact.

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