Modulation of Thy-1 alloantibody responses: donor cell-associated H-2 inhibition and augmentation without recipient Ir gene control.

Abstract

In this study we have found that in vivo PFC responses to Thy-1 are strongly modulated by H-2 gene products in at least 2 ways. First, a profound inhibition of primary PFC responses occurs when foreign H-2 antigens are expressed on Thy-1 incompatible donor cells. This interference effect does not reflect a requirement for H-2-restricted antigen presentation by donor cells, since it is also seen using semi-syngeneic antigenic cells that share a full H-2 haplotype with the recipient. Interference acts more profoundly on slower primary responses than on more rapid secondary responses and requires associative recognition of the H-2 and Thy-1 antigens. By contrast, strong augmentation of the anti-Thy-1 response was obtained when foreign H-2 antigens were expressed in the recipient, as shown by a poor response of an H-2k/k recipient to Thy-1.1 on AKR cells (H-2k) compared with high responses of H-2k/b recipients. A gene controlling this phenotype was mapped to the H-2IA or H-2K regions. However, subsequent experiments revealed that donor recognition of recipient H-2 antigens was required for these high responses; thus, an Ir-gene effect was excluded and an 'intimate form' of an allogeneic effect was postulated. Thus, the immune response to Thy-1 is regulated by at least 3 factors acting at the level of the donor cell, including non-H-2 helper alloantigens, H-2 interference, and H-2-associated allogeneic effects.