Genetic and regulatory contributions of the major histocompatibility complex to the developing cytolytic T lymphocyte repertoire.

The specificity repertoire of H-2Kb-specific CTL derived from 10- to 14-day-old neonates was examined. Analogous to the adult repertoire, the neonatal repertoire is composed of a large number of receptor specificities, each of which is represented at a low frequency, as well as a small number of highly recurrent specificities, which thereby serve as repertoire markers. The expression of most specificities appears to be independently regulated during development, resulting in the expression of a different set of recurrent specificities for neonates and adults within the same strain. The neonatal and adult repertoires were also compared with respect to the influence of the MHC on repertoire. Unlike adults, neonates of MHC different congenic strains (B10.D2 and B10.BR) have in common approximately half their recurrent specificities. Additionally, most parental specificities are expressed codominantly in neonatal F1 hybrids. These results may be interpreted as indicating either that 1) some, but not all, receptor genes demonstrate MHC-linked polymorphism and both parental alleles are expressed in F1 neonates, or 2) T receptor genes are nonpolymorphic in MHC congenic strains and the observed MHC-related repertoire differences are attributable to a positive selection mechanism. Since adults of these same strains do not display significant repertoire similarity, it is suggested that this increased repertoire divergence may be the result of encounters with environmental antigens in association with self-MHC antigens.