1998 Fiscal Year Final Research Report Summary
Immunohematologic studies on the SDF-1/CXCR-4 system with monoclonal antibod.
| Project/Area Number |
09671107
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
HORI Toshiyuki Kyoto University, Institute for Virus Research Instructor, ウイルス研究所, 助手 (70243102)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | CXCR-4 / CDF-1 / chemokine / HIV-1 |
|---|
| Research Abstract |
Three mAbs, termed IVR7, AI58, and THS123, were generated and demonstrated to react specifically with human CXCR-4-transfected COS-7 cells. THSl23 could immunoprecipitate a component with an apparent mol wt of 47 kD from CXCR-4^+ cells. Flow cytometric analysis showed that most of the hematopoietic cell lines and some non-hematopoietic cell lines expressed CXCR-4. A fraction of normal peripheral blood mononulcear cells expressed CXCR-4 but neutrophils were negative. Two color analysis revealed that the majority of but not all T cells, virtually all B cells and all moncytes expressed CXCR-4 while it was hardly detectable on NK cells. As to differentiated helper T cells, Th2 but not Th1 expressed CXCR-4. It was also found that IL-4 could induce expression of functional CXCR-4 on Th1. Thus, expression of CXCR-4 is not ubiquitous but rather cell type-specific in hematopoietic cells.
Entry of HIV-1 is initiated by interaction of the envelope protein gp120 with CD4 and one of the relevant chemokine receptors. Although the V3 region of gp120 is speculated to be involved in interaction with chemokine receptors, it is still unclear if the V3 region can directly bind to them. Using synthetic V3 peptides that correspond to the V3 regions of gp120 of T-tropic, M-tropic and dual tropic HIV-1, we could demonstrate that V3 peptides of T-tropic and dual tropic strains but not that of an M-tropic strain could directly bind to CXCR-4, which indicate that the V3 region of gp120 can bind to the relevant chemokine receptor by itself without CD4 or other domains of gp120.
|
