Abstract

We have studied the effect of mutations in H-2Kb on recognition of Moloney virus antigens by Kb-restricted Moloney virus-specific cytotoxic T lymphocytes (CTL) generated from H-2Db-mutant B6.C-H- 2bm13 ( bm13 ) mice. On the basis of the bm13 virus-specific recognition pattern of a series of Kb-mutant virus-infected (V+) cells, these Kb mutants could be divided into two groups that either shared the relevant H-2K restriction specificities with H-2Kb ( bm3 , bm5 , bm6 , and bm11 ) or lacked them completely (bm1) and/or almost completely ( bm8 ). In the study presented in this report, we concentrated on the alloreactive CTL included in the repertoire of bm13 Moloney-specific CTL. These CTL lysed noninfected (V-) allogeneic target cells of many H-2 types, including all Kb-mutant cells tested (bm1, bm3 , bm5 , bm6 , bm8 , and bm11 ). Recognition of V- cells of two Kb mutants, bm3 and bm11 , which share a common amino acid substitution at position 77 of the H-2K molecule with an additional change at position 89 in bm3 , was compared with recognition of the other Kb-mutant V- target cells in cold target inhibition studies. These studies showed that bm3 and bm11 cells share a determinant or determinants on the H-2K molecule recognized by alloreactive CTL among the Moloney virus-specific CTL population not present on the other Kb-mutant cells; lysis of both target cells was inhibited only by bm3 and bm11 V- cells. On the other hand, lysis of bm3 V+ target cells by bm13 virus-specific CTL was inhibited by all Kb-mutant V+ cells ( bm3 , bm5 , bm6 , and bm11 ) that were killed virus specifically by bm13 CTL. Thus, common determinants on the H-2K molecule of these Kb-mutant V+ cells are recognized by Kb-restricted Moloney virus-specific CTL. From the difference in inhibition pattern of the lytic reaction against bm3 V+ vs bm3 V- cells, we conclude that determinants on the same H-2K molecule recognized by Moloney virus-specific CTL and allocross -reactive effector cells included in the Moloney virus-specific population are not identical.

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