The origin of strain-specific differences in the specificity repertoires of murine cytolytic T lymphocytes.

Abstract

Previous studies, in which fine specificity analysis of CTL clones specific for the H-2Kb alloantigen was used to identify and distinguish the receptor of each clone, demonstrated that the composition of the CTL repertoire is influenced by at least two polymorphic genetic regions, the MHC and the IgH. By using double parent radiation chimeras of the type A + B----(A X B)F1, in which A and B differ at the MHC, it was found that the specificity repertoires of A and B, which normally differ in conventional mice of these strains, were very similar when CTLp were obtained from double parent chimeras. Therefore, the influence of MHC on repertoire was attributable to the environment in which the T cell developed rather than to an intracellular event. In the current study, this same strategy was used to determine whether IgH exerts its influence on the CTL repertoire at the environmental level as well. Double parent chimeras where constructed by using stem cells of BALB/c and B10.BR origin. Not only do these cells differ at the MHC, they also differ polymorphically at a large number of genetic regions including IgH and possibly T alpha structural genes. The results indicated that despite these genetic differences, the specificity repertoires of CTLp representative of the two different genotypes in the chimeras were very similar. Therefore, T cell repertoire differences that arise due to IgH polymorphism are determined by the developing environment. Additionally, these results suggest further that any genetic polymorphism which may exist within the T alpha gene complexes of these strains does not result in differences that can be detected within the CTL response to the Kb alloantigen.