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 their 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 strain STS and 87. 5% genes of the intermediate responder strain BALB/c. Differences in the magnitude of anti-CD3-induced response among CcS/Dem strains indicated that in addition to Fcgamma receptor 2 (Fcgr2) other genes are involved in the control of this response as well, and we have already mapped loci Tria1 (T cell receptor-induced activation 1), Tria2, and Tria3. In order to map additional Tria genes, we tested F2 hybrids between the high responder RC strain CcS-9 and the low responder strain CcS-11. Proliferation in complete RPMI medium without anti-CD3 is controlled by locus Sprol1 (spontaneous proliferation 1) linked to the marker D4Mit23 on Chr 4. At concentration 0.375 microg/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 concentration of mAb, 3 microg/ml, was controlled by Tria5, which mapped to the marker D9Mit15 on Chr 9. Anti-CD3 is being used for modulation of lymphocyte functions in transplantation reactions and in cancer treatment. Study of mechanisms of action of different Tria loci could lead to better understanding of genetic regulation of these reactions.
Havelková
H
H
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Fleming. nám. 2, 16637 Praha 6, Czech Republic.
Kosarová
M
M
Krulová
M
M
Demant
P
P
Lipoldová
M
M
D000818:Animals; D002455:Cell Division / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000737:chemistry*