Mutations inH-2Kbinfluence the specificity of alloreactive effector cells included in the repertoire ofH-2Db-restricted cytotoxic T lymphocytes against Moloney leukemia virus
✍ Scribed by Marijke J. Stukart; Jolande Boes; Cornelis J. M. Melief
- Publisher
- Springer-Verlag
- Year
- 1983
- Tongue
- English
- Weight
- 579 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0093-7711
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✦ Synopsis
Moloney leukemia virus-specific cytotoxic T lymphocytes (CTL), generated by secondary in vitro stimulation of spleen cells with syngeneic virusinfected cells, frequently lysed not only syngeneic virus-infected cells, but also noninfected allogeneic target cells. This phenomenon was studied with B6(H-2 b) responder cells and a series ofH-2Kb-mutant responder cells. Thus, B6 Moloneyspecific CTL lysed noninfected Kb-mutant cells, but not B6 cells, whereas K bmutant Moloney-specific CTL lysed noninfected B6 cells and not noninfected cells of the same mutant. Cold-target-inhibition studies showed that the CTL reactions against different allogeneic cells were mediated by different subpopulations of virus-specific CTL: lysis of allogeneic target cells was fully inhibited only by the same allogeneic and by syngeneic virus-infected cells, but not by another allogeneic cell, also lysed by the same effector-cell population. Lysis of syngeneic virus-infected cells could not be inhibited by allogeneic target cells. These data imply that a minority of virus-specific CTL shows crossreactivity with a given allogeneic target cell. It is concluded that limited amino acid substitutions in the K b molecule alter the repertoire of Moloney virusspecific CTL, as reflected in alloreactive CTL populations, even though the virus-specific CTL response of B6 and all K b mutants is mainly Db-restricted. Thus, the development of tolerance to self class-I major histocompatibility complex (MHC) molecules affects the repertoire of self-restricted eytotoxic T cells.