Influence of the major histocompatibility complex on the repertoire of allospecific cytolytic T lymphocytes

Superimposed on the heterogeneous anti-H-2Kb cytolytic T lymphocyte (CTL) receptor repertoire of allogeneic murine strains are reactivities that recur with high frequency amongst individuals of any given strain. These receptor specificities represent phenotypic markers of the CTL repertoire and, as such, have been used to compare receptor repertoires of genetically disparate strains. The results demonstrate that congenic strains differing only in the MHC (B10.D2 and B10.BR) differ significantly in their H-2Kb-specific CTL repertoires. This finding clearly demonstrates a role for the MHC in determination of the CTL precursor repertoire. The mechanism by which MHC influences CTL specificity was explored through analysis of the anti-H-2Kb repertoire of (B10.BR X B10.D2)F1 hybrids. Because at least one recurrent parental specificity has found to be recurrent in F1 progeny as well, the findings indicate that MHC-specific tolerance cannot be solely responsible for repertiore differences between MHC-disparate strains. In addition, the F1 repertoire is characterized by the emergence of several nonparental recurrent specificities.