Genetic control of the immune response to myoglobins. IV. Inhibition of determinant-specific Ir gene-controlled antigen presentation and induction of suppression by pretreatment of presenting cells with anti-Ia antibodies
Berzofsky, J.A.; Richman, L.K.
Journal of Immunology 126(5): 1898-1904
1981
ISSN/ISBN: 0022-1767 PMID: 6163822 Document Number: 170784
It is reported that macrophages, preincubated with antigen and extensively washed, can present myoglobin or its fragments to myoglobin-primed T cells to induce proliferation in vitro, and that this presentation is under the Ir gene control. Furthermore, the dose-response curve for T-cell proliferation could be explained by the amount of antigen taken up by the antigen-presenting macrophage at that concentration rather than by a direct effect on the responding T cells. Anti-Ia molecules encoded in the IA and IC subregions of the macrophages blocked the ability of these cells to present antigen when the antibodies were present only during pretreatment of the macrophages with antigen, and then washed out. Conversely, antibodies directed against H-2K/H-2D region determinants, although able to bind to the Kuppfer cells, failed to block their ability to present myoglobin. Antibodies against the IA-encoded molecule inhibited the response even when the only high responder allele involved mapped in IC. This result suggested that T cell recognition of IA-encoded molecules is necessary for cell interaction regardless of whether or not Ir gene control maps to this region. [For Pt. III see ABA 48, 6196].