T-cell proliferative response is controlled by loci Tria4 and Tria5 on mouse Chromosomes 7 and 9

Lymphocytes of mouse strains BALB/cHeA (BALB/c) and STS/A (STS) differ in t heir response to CD3 antibody (anti-CD3). We analyzed the genetic basis of this strain difference, using the Recombinant Congenic Strains (RCS) of the BALB/c-c-STS/Dem (CcS/Dem) series. Each of the 20 CcS/Dem strains carries a different, random combination of 12.5% genes from the nonresponding strai n STS and 87.5% genes of the intermediate responder strain BALB/c. Differen ces in the magnitude of antiCD3-induced response among CcS/Dem strains indi cated that in addition to Fc gamma receptor 2 (Fcgr2) other genes are invol ved in the control of this response as well, and we have already mapped loc i Tria1 (T cell receptor-induced activation 1), Tria2, and Tria3. In order to map additional Tria genes, we tested F-2 hybrids between the high respon der RC strain CcS-9 and the low responder strain CcS-11. Proliferation in c omplete RPMI medium without anti-CD3 is controlled by locus Sprol1 (spontan eous proliferation 1) linked to the marker D4Mit23 on Chr 4. At concentrati on 0.375 mu g/ml anti-CD3 mAb, the response was controlled by a locus Tria4 , which maps to the marker D7Mit32 on Chr 7. The response to the higher con centration of mAb, 3 mu g/ml, was controlled by Tria5, which mapped to the marker D9Mir15 on Chr 9. Anti-CD3 is bring used for modulation of lymphocyt e functions in transplantation reactions and in cancer treatment. Study of mechanisms of action of different Tria loci could lead to better understand ing of genetic regulation of these reactions.