The CTL Recognition of HIV-1 and the CTL-escape mechanism of HIV-1


Human CD8 T cell differentiation


Molecular recognition of virus antigenic epitopes by T cell receptor


CTL recognition of hepatitis virus

I. The CTL Recognition of HIV-1 and the CTL-escape mechanism of HIV-1
When a virus infection is established, helper T cells recognize it via antigen presenting cells, inducing CTL responses and production of specific antibodies. Usually, induction of CTLs takes place at least in a week after the infection. By the time, production of antibodies is seen reaching its peak in 2 weeks in many cases of viral infections. CTLs recognize and kill virus-infected cells, preventing viral replication. Antibodies, on the other hand, particularly neutralizing antibodies, inactivate a virus, by binding to virus particles in blood and on tissues. Also, NK cells are known to recognize and kill virus-infected cells. Thus, a virus is being eliminated from the body.
Meanwhile, in HIV-1 infection, there is a temporary fall in CD4+ T cell count during the early stage of infection. This is because CD4+ T cells are target cells of HIV-1. The number, however, gets back to its normal in most cases since CTLs eradicate HIV-1-infected CD4+ T cells. Production of antibodies is seen relatively late, sometimes, in a month or two after the infection. What makes HIV-1 infection unique is that the virus cannot be completely eradicated by the immune system, persisting in the body, eventually increasing viral loads, and thus developing AIDS. Persisting low level of viral loads may explain that cellular immunity partially inhibits viral replication. Nevertheless, the immune system is unable to eradicate a virus completely, and the virus reverts to replicating after a certain period of time. The mechanism to explain these is yet to be clarified. For this reason, we are trying to clarify the mechanism by which cellular immunity recognizes HIV-1, and HIV-1 evades cellular immunity. Based on the results of these researches, we will promote establishment of AIDS therapy and vaccine development.
Identification of HIV-specific CTL epitopes
Nef-mediated downregulation of surface expression of HLA class I molecules and its effect on HIV-1-specific CTL escape of HIV-1 
Analysis of HIV-1- specific CD8 T cells in patients with HIV-1  

II. Human CD8 T cell differentiation
There is a hypothesis to explain CTL escape mechanism of HIV-1 that functional disorder due to abnormality of HIV-1 specific CD8 T cell differentiation may be the culprit. The mechanism of peripheral CD8 T cell differentiation, however, has not been completely clarified to understand differences in differentiation between normal CD8 T cells and HIV-specific CD8 T cells. Therefore, we first made a differentiation or maturation analysis on normal human peripheral CD8 T cell, and from there we attempted to examine the possibility of differentiation or maturation abnormality of HIV-1-specific CD8 T cells in HIV-1 infected patients.
Surface expression of chemokine receptors and CD8 T cell differentiation
CD8 T cell differentiation stages and its function in each stage  

VDMolecular recognition of virus antigenic epitopes by T cell receptor
Viruses including HIV-1 are processed into peptides and presented to CD8 T cells via HLA class I molecules, leading to T cell recognition. T cells recognize virus peptides combined with HLA class I molecules on cell surface with T cell receptor. We are studying T cell receptor-mediated recognition of the peptides binding to HLA class I molecules to reveal recognition mechanism against diverse viruses in human.
TCR analysis on HIV recognition  
Analysis of TCR at the protein level and its recognition of HLA-peptide complex 

WDCTL recognition of hepatitis virus
Many cases of HCV co-infection among HIV-1 positive patients have been reported, particularly among those infected by transfusion of blood and serum products.
Concerns of developing chronic hepatitis, cirrhosis, and liver cancer are growing for patients who show certain progress in controlling the onset of AIDS after receiving HAART. For this reason, we studied the CTL recognition of hepatitis B/C to identify the mechanism by which hepatitis becomes chronic.

CTL recognition of hepatitis B  
CTL recognition of hepatitis C