Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-Ak reagent blocks helper T cell recognition of self major histocompatibility complex determinants.

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Abstract
The functional role of cell surface Ia antigens was studied for in vitro antibody responses, using as a probe the ability of anti-Ia reagents to inhibit these responses. A hybridoma monoclonal anti-Ia reagent specific for a product of I-Ak (Ia. 17) profoundly inhibited in vitro antibody responses to TNP-KLH [trinitrophenyl-keyhole limpet hemocyanin] by [murine] spleen cells of the I-Ak, but not I-Ab haplotype. Anti-I-Ak inhibition occurred as a result of interaction with an accessory cell I-Ak product, but not by interaction with T or B cell product, in spite of the fact that functional B cells, as well as accessory cells, could express the determinant detected by this hybridoma reagent. Apparently the Ia expressed by accessory cells is of unique functional importance in these responses. To further characterize the function of Ia antigens in this response system, the anti-I-Ak inhibition mechanism was determined. The inhibition resulting from anti-I-Ak interaction with accessory cell Ia was not mediated by nonspecific suppressor cells, nor was there nonspecific interference with accessory cell function as a result of the anti-Ia antibody binding. The relationship between anti-Ia inhibition and T helper cell recognition of self determinations on accessory cells was analyzed using T cells from radiation bone marrow chimeras: (B10 .times. B10.A)F1 .fwdarw. B10 (F1 .fwdarw. B10) chimera T cells were able to cooperate with B10 (H-2b), and I-Ab), but not B10.A (H-2a and I-Ak) accessory cells for responses to TNP-KLH; F1 .fwdarw. B10.A T cells were able to cooperate with B10.A, but not B10 accessory cells; both chimera populations were able to cooperate with (B10 .times. B10.A)F1 (F1) accessory cells; monoclonal anti-I-Ak inhibited the cooperation of F1 .fwdarw. B10.A T cells with F1 accessory cells, but had no effect upon the cooperation of F1 .fwdarw. B10 T cells with the same F1 accessory cells. Thus, inhibition by anti-I-Ak is dependent upon active helper T cell recognition of I-Ak-encoded determinants expressed on accessory cells. Evidently T cells recognize self Ia determinants expressed on accessory cells, and such recognition is required for the generation of T cell dependent antibody responses.