|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1996 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1995 : ¥1,000,000 (Direct Cost : ¥1,000,000)
To examine the changes in CD4^+ T cells after HTLV-I infection, we have performed differential hybridization of a cDNA library, using probes obtained from an ATL cell line as well as probes obtained from normal CD4^+ T cells and the Molt-4 cell line. By differential screening of this library, thirty clones were isolated. These genes were as follows : 6 membranous proteins, 5 oncogenes, 7 cytokines, 2 transcription factors, 6 cellular proteins and 4 unknown genes.
Of these genes, SFA-1 (CD151) was a novel member of transmembrane 4 superfamily. The mRNA of the SFA-1 gene is approximately 1.6 kb in size and encodes a protein of 253 amino acids. Expression of SFA-1 gene was either absent or present at a low level in lymphoid cells but was up-regulated after HTLV-I transformation and transactivated by Tax. SFA-1 was broadly expressed in many human cell types and conserved in mouse. Next, we have analyzed the adhesion molecules associated with, and the biological function of SFA-1/PETA-3 (CD1
51) in HTLV-I-infected T cells and in freshly isolated ATL cells using anti-SFA-1 (CD151) monoclonal antibody. The CD151 molecule was associated with the alpha5beta1 integrin molecule and it enhanced alpha5beta1 integrin-mediated adhesion to fibronectin. In addition, the expression levels of CD151, alpha4beta1 integrin and alpha5beta1 integrin on ATL cells from lymph nodes of lymphoma-type ATL patients were significantly higher than those on circulating ATL cells from leukemia-type ATL patients.
SFA-2 is a novel bZIP transcription factor. The mRNA of the SFA-2 gene is approximately 0.9 kb in size and encodes a protein of 125 amino acids, containing a basic region-leucine zipper DNA-binding domain. The SFA-2 gene was strongly expressed in mature T and B lymphocytes, and was up-regulated after transformation of HTLV-I.The SFA-2 did not homodimerize efficiently but formed heterodimer preferentially with c-Jun. The SFA-2/c-Jun heterodimer bound preferentially to the AP-1 and CRE sites.
ストレス蛋白の一つであるCalreticulinはHTLV-I感染にて発現が増強し、過剰発現した細胞はHTLV-I感染を増強させ、これはα integrinを介することが明らかとなった。また、私どもが単離したクローン8-46は4回膜貫通型でマウスのレトロウイルスレセプターと一部homologyがありHTLV-Iのレセプターの可能性があり、現在、transformantを作成し、検討している。 Less