PMID- 9339848 OWN - NLM STAT- MEDLINE DCOM- 19971208 LR - 20061115 IS - 0889-2229 (Print) IS - 0889-2229 (Linking) VI - 13 IP - 15 DP - 1997 Oct 10 TI - HIV type 1 envelope glycoprotein 120 carboxy-terminal peptide-induced human T cell lines selectively suppress heterogeneous proliferative T cell responses to soluble antigens. PG - 1313-24 AB - It has been proposed that the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope gp120 carboxy-terminal sequence, TKAKRRVVEREKR (CT120), may represent a functional mimic of the human leukocyte antigen (HLA) class II DR beta-chain third hypervariable region (HVR3) sequence motif located at position 69-81. Presentation of this potentially pathogenic fragment by HLA class I and/or II molecules, in a manner analogous to the indirect pathway of allorecognition, may induce both widespread cellular activation and also break self-tolerance, resulting in the selective and progressive anti-self HLA class II-directed immune suppression, which is a central feature of HIV-1 infection and the associated acquired immune deficiency syndrome (AIDS). To investigate the functional role of the HIV-1 gp120 C-terminal fragment T cell lines (TCLs) were raised from three healthy HIV-1-seronegative subjects at low risk of HIV-1 exposure, by repeated stimulation with a short synthetic 13-mer CT120 peptide in vitro. Graded concentrations (10[3] to 5 x 10[4]) of CT120 TCLs suppressed the primary 6-day proliferation of autologous PBMCs in response to the soluble antigens tetanus toxoid (TT) and purified protein derivative (PPD). In contrast, CT120 TCLs demonstrated no suppressive effect on 3-day phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM) mitogenic responses. Fractionation of CT120 TCLs into highly purified CD4+ and CD8+ T cell subsets demonstrated that the CD8+ T cell fraction mediated the suppressor effector function. HLA restriction analysis revealed a complex pattern as both anti-HLA class II DR and anti-HLA class I (A, B, C) MAbs inhibited proliferation of oligoclonal CD8+ CT120 TCLs. Strategies aimed at specifically inhibiting such putative immunopathogenic HIV-1-encoded T cell epitopes may be an important consideration for development of future HIV-1 immunotherapy. FAU - Wilson, S E AU - Wilson SE AD - Academic Virology, The London Hospital Medical College, UK. swilson@hivnet.fhcrc.org FAU - Habeshaw, J A AU - Habeshaw JA FAU - Addawe, M A AU - Addawe MA FAU - Hounsell, E F AU - Hounsell EF FAU - Oxford, J S AU - Oxford JS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - AIDS Res Hum Retroviruses JT - AIDS research and human retroviruses JID - 8709376 RN - 0 (Antibodies, Blocking) RN - 0 (Epitopes) RN - 0 (HIV Envelope Protein gp120) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Peptides) RN - 0 (Phytohemagglutinins) RN - 0 (Pokeweed Mitogens) RN - 0 (Tetanus Toxoid) RN - 0 (Tuberculin) RN - 11028-71-0 (Concanavalin A) SB - IM MH - Adult MH - Amino Acid Sequence MH - Antibodies, Blocking/immunology MH - Autoimmunity MH - CD8-Positive T-Lymphocytes/immunology MH - Cell Division MH - Cells, Cultured MH - Concanavalin A/immunology MH - Cross Reactions/immunology MH - Dose-Response Relationship, Immunologic MH - Epitope Mapping MH - Epitopes/immunology MH - HIV Envelope Protein gp120/*immunology MH - HIV Infections/*immunology MH - HIV Seronegativity MH - HIV-1/*immunology MH - Histocompatibility Antigens Class I/immunology MH - Histocompatibility Antigens Class II/immunology MH - Histocompatibility Testing MH - Humans MH - Immune Tolerance MH - Leukocytes, Mononuclear/immunology MH - Middle Aged MH - Molecular Sequence Data MH - Peptides/chemical synthesis/*immunology MH - Phytohemagglutinins/immunology MH - Pokeweed Mitogens/immunology MH - T-Lymphocyte Subsets/immunology MH - T-Lymphocytes/cytology/*immunology MH - Tetanus Toxoid/immunology MH - Tuberculin/immunology EDAT- 1997/10/27 00:00 MHDA- 1997/10/27 00:01 CRDT- 1997/10/27 00:00 PHST- 1997/10/27 00:00 [pubmed] PHST- 1997/10/27 00:01 [medline] PHST- 1997/10/27 00:00 [entrez] AID - 10.1089/aid.1997.13.1313 [doi] PST - ppublish SO - AIDS Res Hum Retroviruses. 1997 Oct 10;13(15):1313-24. doi: 10.1089/aid.1997.13.1313.