accumulation of specific amino acid substitutions in hla-b35-restricted human immunodeficiency virus type 1 cytotoxic t lymphocyte epitopes.

NLM AIDSLINE Accumulation of specific amino acid substitutions in HLA-B35-restricted human immunodeficiency virus type 1 cytotoxic T lymphocyte epitopes. Kawana A; Tomiyama H; Takiguchi M; Shioda T; Nakamura T; Iwamoto A;
November 30, 1999

AIDS Res Hum Retroviruses. 1999 Aug 10;15(12):1099-107. Unique 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 ARTICLE Amino Acid Sequence Amino Acid Substitution Base Sequence Clone Cells DNA Primers Epitopes/CHEMISTRY Human HIV-1/IMMUNOLOGY HLA-B35 Antigen/CHEMISTRY/IMMUNOLOGY Molecular Sequence Data Sequence Homology, Amino Acid Support, Non-U.S. Gov't T-Lymphocytes, Cytotoxic/IMMUNOLOGY

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Information in this article was accurate in November 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.