Effects of blocking helper T cell induction in vivo with anti-Ia antibodies. Possible role of I-A/E hybrid molecules as restriction elements.

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Abstract
To examine the role of Ia antigens in controlling T cell activation in vivo, unprimed (CBA .times. B6)F1 (H-2k .times. H-2b) T cells were positively selected to sheep erythrocytes (SRC) for 5 days in irradiated F1 mice in the presence of large doses of anti-Iak antibody. With selection in the presence of broad-spectrum anti-Iak antibody (A.TH anti-A.TL antiserum), the activated T cells were markedly reduced in their capacity to collaborate with B10.BR (I-Ak I-bk I-Jk I-Ek I-Ck) (kkkkk) or B10.A (4R) (kbbbb) B cells but gave good helper responses with B10 (bbbbb) and (B10 .times. B10.BR)F1 B cells. Because there was no evidence for suppression, these findings imply that the anti-Iak antibody bound to Ia determinants on radioresistant macrophage-like cells of F1 host origin and blocked the activation of the Iak-restricted subgroup of F1 T cells but did not affect activation of the Iab-restricted T cell subgroup. Analogous experiments in which F1 T cells were selected in SRC in F1 mice in the presence of monoclonal anti-I-Ak antibody gave different results. In this situation, the reduction in T cell help for Iak-bearing B cells applied to B10.A(4R) B cells but not to B10.BR B cells. With selection of F1 T cells in B10.A(4R) mice, anti-I-Ak antibody blocked T cell help for B10.A(4R) and B10.BR B cells. Apparently, genes telomeric to the I-A subregion were involved in controlling T cell activation and T-B collaboration. Because no evidence could be found that I-B through I-C determinants per se could act as restrictions elements, the working hypothesis is that Iak-restricted T cells consist of 2 subgroups of cells: one subgroup is restricted by I-A-encoded molecules, whereas the other is restricted by I-A/E hybrid molecules encoded by 2 separated genes situated in the I-A and I-E subregions, respectively. The notion that A/E hybrid molecules serve as restriction elements confirms that these molecules can act as alloantigens and control responses to certain antigens under double Ir gene control.