title: Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants.
abstract: Most asymptomatic individuals infected with HIV-1 have a cytotoxic T lymphocyte (CTL) response to the virus Gag proteins which can be demonstrated in vitro. Epitopes have been mapped in p17 Gag and p24 Gag restricted by HLA-B8 (p17-3 and p24-13) and -B27 (p24-14). Viruses isolated from patients who make CTL responses to these peptides vary within the genetic sequences encoding these epitopes and some mutations lead to reduction in killing activity in vitro. This was attributed to either failure of the variant epitope to bind major histocompatibility complex class I or failure of T-cell receptors to bind the presented peptide. But peptide variants of class I-restricted epitopes cause 'antagonism', that is, the presence of a variant epitope (in the form of peptide) inhibits normal lysis of targets presenting the original epitope. This mirrors similar findings in class II-restricted systems. Here we report that naturally occurring variant forms of p17-3, p24-13 and p24-14 may cause antagonism of CTL lines derived from the same individuals. The effect is present if the epitopes are derived from synthetic peptides and when they are processed from full-length proteins expressed by either recombinant vaccinia constructs or replicating HIV.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, UK.
authors.forename: P
authors.initials: P
authors.lastname: Klenerman
authors.forename: S
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: S
authors.initials: S
authors.lastname: McAdam
authors.forename: J
authors.initials: J
authors.lastname: Edwards
authors.forename: S
authors.initials: S
authors.lastname: Daenke
authors.forename: D
authors.initials: D
authors.lastname: Lalloo
authors.forename: B
authors.initials: B
authors.lastname: Köppe
authors.forename: W
authors.initials: W
authors.lastname: Rosenberg
authors.forename: D
authors.initials: D
authors.lastname: Boyd
authors.forename: A
authors.initials: A
authors.lastname: Edwards
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015795:HLA-B8 Antigen / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D000939:Epitopes; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015795:HLA-B8 Antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1