Abstract:
:HLA is one of the genetic factors that influence the clinical course of HIV-1 infection, and patients with HLA-B35 are prone to rapid disease progression. Nine viral epitopes that are recognized by cytotoxic T lymphocytes (CTLs) in an HLA-B35-restricted manner were determined. To examine how HIV-1 sequences are selected by CTLs in vivo, we sequenced the nine CTL epitopes of the virus in patient plasma. Here we show that certain amino acid substitutions at three epitopes were observed with significantly higher frequency in HLA-B35-positive patients than in HLA-B35-negative patients. By performing experiments with CTL clones established from the HLA-B35-positive patients, it was determined that one of the three substitutions was probably an escape mutation. However, concerning the other two epitopes, representative CTL clones killed target cells pulsed with mutant peptides as efficiently as those pulsed with wild-type peptides, suggesting that CTLs that can be established in vitro are not functioning properly in vivo. Amino acid sequence drift in all HLA-B35-restricted epitopes was rare during the observation period (1 year). Our results may have relevance in understanding the rapid clinical progression in HLA-B35-positive patients.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Kawana A,Tomiyama H,Takiguchi M,Shioda T,Nakamura T,Iwamoto Adoi
10.1089/088922299310395subject
Has Abstractpub_date
1999-08-10 00:00:00pages
1099-107issue
12eissn
0889-2229issn
1931-8405journal_volume
15pub_type
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journal_title:AIDS research and human retroviruses
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