H-2-linked genes determine the level of the primary in vitro anti-Mls response

Abstract

The level of cell proliferation and interleukin-2 (IL-2) production observed in an anti-Mls mixed lymphocyte reaction between spleen cells from H-2 compatible, Mls incompatible mouse strains is determined by the H-2 haplotype of the mouse combination. Thus, while AKR (H-2k) spleen cells stimulated strong Mlsa responses in H-2k responder cells, AKR-H-2b spleen cells stimulated no or negligible Mlsa responses in responder cells from H-2b mouse strains. This effect was observed at the levels of IL-2 production and cell proliferation. The magnitude of the response observed using F1 (H-2k/H-2b) responder cells was found to be a function of stimulator rather than responder cells. The poor stimulatory capacity of AKR-H-2b spleen cells was also shown not to be due to the loss of the stimulatory Mlsa allele during the construction of the congenic strain from AKR and C57BL/6 parental strains. Using stimulator cells from a second series of congenic mice, we found H-2b (strain D1.LP) again to represent a poorly Mlsa stimulatory H-2 haplotype. In addition, H-2q (DBA/1) cells displayed very poor Mlsa stimulatory potential while H-2d (D1.C) cells were efficient Mlsa stimulators. Again the effect was shown to be at the level of the stimulator cells. In toto, our findings indicate that the H-2k and H-2d haplotypes encode strong Mlsa stimulatory potential while the H-2b and H-2q haplotypes determine poor Mlsa stimulatory potential in primary in vitro responses, measured as cell proliferation and IL-2 production.