Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes.

Journal article

A major advance in understanding human immunodeficiency virus (HIV) biology was the discovery that the beta-chemokines MIP-1 alpha (macrophage inflammatory protein-1 alpha), MIP-1 beta (macrophage inflammatory protein-1 beta) and RANTES (regulated on activation, normal T-cell expressed and secreted) inhibit entry of HIV-1 into CD4+ cells by blocking the critical interaction between the CCR5 coreceptor and the V3 domain of the viral envelope glycoprotein gp120 [1,2]. CD8+ lymphocytes are a major source of beta-chemokines [3], but the stimulus for chemokine release has not been well defined. Here, we have shown that engagement of CD8+ cytotoxic T lymphocytes (CTLs) with HIV-1-encoded human leukocyte antigen (HLA) class I-restricted peptide antigens caused rapid and specific release of these beta-chemokines. This release paralleled cytolytic activity and could be attenuated by naturally occurring amino acid variation within the HLA class I-restricted peptide sequence. Epitope variants that bound to appropriate HLA class I molecules but failed to stimulate cytolytic activity in CTLs also failed to stimulate chemokine release. We conclude that signalling through the T-cell receptor (TCR) following binding of antigen results in beta-chemokine release from CTLs in addition to cytolytic activity, and that both responses can be abolished by epitope mutation. These results suggest that antigenic variation within HIV-1 might not only allow the host cell to escape lysis, but might also contribute to the propagation of infection by failing to activate beta-chemokine-mediated inhibition of HIV-1 entry.

Authors: Price, D; Sewell, A; Dong, T; Tan, R; Goulder, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Current biology : CB
• Volume: 8
• Issue: 6
• Pages: 355-358
• Publication date: 1998-03-01
• DOI: 10.1016/s0960-9822(98)70138-1
• EISSN: 1879-0445
• ISSN: 0960-9822
• Language: English
• Keywords: Peptides; Macrophage Inflammatory Proteins; Chemokine CCL4; HIV-1; Polymerase Chain Reaction; HLA Antigens; Chromatography, High Pressure Liquid; Humans; Chemokine CCL5; Epitopes, T-Lymphocyte; T-Lymphocytes, Cytotoxic; Chemokines, CC