The T lymphocyte proliferative response to poly-L-Glu-poly-D,L-Ala--poly-L-Lys

The immune response to several antigens has been shown to be under the control of two complementing major histocompatibility-linked immune response (Ir) genes. In most cases, one gene has been mapped to the I-A subregion and the other to the I-E/C subregion. However, in some cases F1 complementation has been described between two alleles in the I-A subregion, so called beta-beta complementation. In these examples, complementation has been seen at the antibody level but not in a T lymphocyte proliferation assay. In the present work, we studied the T cell proliferative response to poly-L-Glu-poly-D,L-Ala--poly-L-Lys (G-A--L). Peritoneal exudate, T lymphocyte-enriched subpopulations (PETLES) from F1 hybrids between C57BL/10 and B10.A, C57BL/10, and B10.A(4R), or B10.A and B10.A(3R) or (5R) mice responded well to G-A--L. In contrast, PETLES from F1 hybrids between C57BL/10 and B10.A(5R) or B10.A and B10.A(4R) mice, as well as from all inbred strains tested, failed to respond to G-A--L. These results demonstrate for the first time an example of Ir gene complementation at the T cell level in which both genes map to the left of the I-J subregion presumably in I-A. This system should now allow us to determine whether alpha-beta and beta-beta complementation take place through the same biologic mechanism.