Effects of HLA-antigen presentation machinery on the antiviral effectiveness of T lymphocytes.
| Project/Area Number |
17590419
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Virology
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
UENO Takamasa Kumamoto University, Center for AIDS Research, Lecturer, エイズ学研究センター, 講師 (10322314)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKIGUCHI Masafumi Kumamoto University, Center for AIDS Research, Professor, エイズ学研究センター, 教授 (00183450)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
|
|---|
| Keywords | Antigen / T lymphocyte / T cell receptor / HIV / AID S / antiviral activity / MHCクラスI / 細胞傷害性T細胞 / 抗原提示 / 抗体 / ファージディスプレイ |
|---|
| Research Abstract |
A less effective HIV-specific cytotoxic T lymphocyte (CTL) response during a chronic HIV infection is an important factor for progressive immunopathogenesis, but how such CTLs are generated and accumulated remains elusive. Herein, we characterized CTL responses toward Pol, Env, and Nef optimal epitopes presented by HLA-B^*35, a human leukocyte antigen (HLA) associated with rapid disease progression. We found CTL escape variants within Pol and Nef epitopes that affected recognition by T cell receptors, although there was no mutation within the Env epitope. Analysis of peptide-HLA tetrameric complexes revealed that CD8 T cells exclusively specific for the Nef variant were generated following domination by the variant viruses. The variant-specific cells were capable of secreting antiviral cytokines but showed impaired antigen-specific proliferative responses ex vivo, whereas wild-type-specific ones had potent activities. Moreover, clonotypic CD8 T cells specific for the Pol variant showed diminished proliferation, whereas Env-specific ones had no functional he terogeneity. Taken together, our data indicate that antigenic variations that lead to a loss of T cell receptor recognition result not solely in the escape from established CTL responses, but also in decoy antigens that recruit less effective HlV-specific CTLs. Such a decoy antigen could have in part an actively negative effect on antiviral immune responses during a chronic HIV infection, providing us insights into the progressive immunopathogenesis as well as vaccine design against HIV infections.
|
Report
(3 results)
Research Products
(8 results)
