Dating progressing slowly
HLA class I-peptide tetrameric complexes (tetramers) were synthesized as described previously (2).
Four HIV-1 specific epitopes (Pol283-8, Pol743-9, Gag327-8, and Rev71-11) (45) were used for the refolding of HLA-B*5101 molecules.
HLA-B*5101 hemophiliacs exhibited significantly slow progression. The analysis of HLA-B*5101-restricted HIV-1-specific cytotoxic T-lymphocyte (CTL) responses to 4 HLA-B*-restricted epitopes in 10 antiretroviral-therapy (ART)-free HLA-B*5101 hemophiliacs whose HIV-1 replication had been controlled for approximately 25 years had HIV-1 possessing the wild-type Pol283-8 sequence or the Pol283-8V mutant, which does not critically affect T-cell recognition, whereas other HLA-B*5101 hemophiliacs had HIV-1 with escape mutations in this epitope.
The results suggest that the control of HIV-1 over approximately 25 years in HLA-B*5101-positive hemophiliacs is associated with a Pol283-8-specific CD8 T cells play a critical role in the control of HIV-1 infections (26, 5), but HIV-1 escape occurs during acute and chronic phases of an HIV-1 infection (6, 14).
In the present study, we analyzed the effect of HLA-B*5101 on clinical outcome in Japanese hemophiliacs infected with HIV-1.
They include the appearance of mutants that escape from HIV-1-specific cytotoxic T lymphocytes (CTLs) (6, 14) and neutralizing antibodies (27, 47, 48), impaired recognition of HIV-1-infected cells by HIV-1-specific CTLs due to Nef-mediated downregulation of HLA class I molecules (8, 42), and impaired function of HIV-1-specific T cells (3).
Phycoerythrin (PE)-labeled streptavidin (Molecular Probes) was used for the generation of the tetramers.
PBMCs were incubated with the tetramers at 37°C for 30 min.
These findings imply that HIV-1-specific CTLs restricted by these alleles may play an important role in the control of HIV-1 replication in LTNPs.
The mechanism of control of HIV-1 replication has been analyzed in LTNPs and slow progressors carrying HLA-B*57/5801, HLA-B*27, or HLA-B*13, and has been related to the Gag-specific CD8 T-cell epitopes presented by these alleles (9, 11, 14, 16, 34).Two Pol-specific CTLs are known to have strong abilities to suppress HIV-1 replication (43).