PMID- 9512422
OWN - NLM
STAT- MEDLINE
DCOM- 19980526
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 8
IP  - 6
DP  - 1998 Mar 12
TI  - Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T 
      lymphocytes.
PG  - 355-8
AB  - 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.
FAU - Price, D A
AU  - Price DA
AD  - Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
FAU - Sewell, A K
AU  - Sewell AK
FAU - Dong, T
AU  - Dong T
FAU - Tan, R
AU  - Tan R
FAU - Goulder, P J
AU  - Goulder PJ
FAU - Rowland-Jones, S L
AU  - Rowland-Jones SL
FAU - Phillips, R E
AU  - Phillips RE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines, CC)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA Antigens)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Peptides)
SB  - IM
MH  - Chemokine CCL4
MH  - Chemokine CCL5/isolation & purification
MH  - Chemokines, CC/*biosynthesis/immunology
MH  - Chromatography, High Pressure Liquid
MH  - Epitopes, T-Lymphocyte/immunology
MH  - HIV-1/*immunology
MH  - HLA Antigens/immunology
MH  - Humans
MH  - Macrophage Inflammatory Proteins/isolation & purification
MH  - Peptides/immunology
MH  - Polymerase Chain Reaction
MH  - T-Lymphocytes, Cytotoxic/*immunology/virology
EDAT- 1998/03/25 00:00
MHDA- 1998/03/25 00:01
CRDT- 1998/03/25 00:00
PHST- 1998/03/25 00:00 [pubmed]
PHST- 1998/03/25 00:01 [medline]
PHST- 1998/03/25 00:00 [entrez]
AID - S0960-9822(98)70138-1 [pii]
AID - 10.1016/s0960-9822(98)70138-1 [doi]
PST - ppublish
SO  - Curr Biol. 1998 Mar 12;8(6):355-8. doi: 10.1016/s0960-9822(98)70138-1.