IL-2-INDUCED PROLIFERATIVE RESPONSE IS CONTROLLED BY LOCI CINDA1 AND CINDA2 ON MOUSE CHROMOSOME-11 AND CHROMOSOME-12 - A DISTINCT CONTROL OF THE RESPONSE INDUCED BY DIFFERENT IL-2 CONCENTRATIONS

Lymphocytes of mouse strains BALB/cHeA (BALB/c) and STS/A (STS) differ in the IL-S-induced proliferative response, STS being a high and BALB /c a low responder in the range of concentrations 125-2000 IE/ml. We a nalyzed the genetic basis of this strain difference using the recombin ant congenic (RC) strains of the BALB/c-c-STS/Dem (CcS/Dem) series. Th is series comprises 20 homozygous strains all derived from two parenta l inbred strains: the ''background'' strain BALB/c and the ''donor'' s train STS. Each CcS/Dem strain contains a different, random set of app roximately 12.5% genes of the donor strain STS and approximately 87.5% genes of the background strain BALB/c. In this way, the STS genes con trolling the LL-a-induced response became separated into individual Cc S/Dem strains, as indicated by differences in the magnitude of the IL- a-induced response among CcS/Dem strains (M. Lipoldova ct al., 1995, I mmunogenetics 41: 301-311). To map some of these genes, we tested Fz h ybrids between one of the high-responder RC strains, CcS-4, and the lo w-responder parental strain BALB/c. We found that the response to high IL-2 concentrations is controlled by a locus, Cinda1 (cytokine-induce d activation 1), on chromosome 11 near the marker D11Mit4. The respons e to a lower dose of IL-2 tested on lymphocytes of the same mice was f ound to be controlled by another locus, Cinda2, in the centromeric par t of chromosome 12, the higher response being linked to the STS allele of the marker D12Mit37. Understanding the action of genetic factors, such as Cinda1 and Cinda2, that control T cell function is expected to contribute to the efficient analysis of the genetic control of suscep tibility to infections and autoimmune diseases. (C) 1997 Academic Pres s.