Carboxyl-terminal and central regions of human immunodeficiency virus-1 NEF recognized by cytotoxic T lymphocytes from lymphoid organs. An in vitro limiting dilution analysis.
Cytotoxic T lymphocytes (CTL) specific for human immunodeficiency virus (HIV) proteins have been analyzed in lymphoid organs from seropositive patients. Indeed, an active HIV replication coexists with a major CD8+ lymphocytic infiltration in these organs. We have shown in a previous report that HIV-seropositive patients lungs were infiltrated by HIV specific CD8+ lymphocytes. In the present report, we show that HIV-specific CTL responses can also be detected in lymph nodes and spleens, and were mainly directed against the ENV, GAG, and NEF HIV-1 proteins. The primary NEF-specific CTL responses were further characterized by epitope mapping. Determination of epitope-specific CTL frequencies were performed by limiting dilution analysis. Our results indicated that, in addition to the central region of NEF (AA66-148), a new immunodominant region is recognized by CTL. This region corresponds to the carboxyl-terminal domain of NEF (amino acids 182-206). AA182-206 is recognized in association with at least two common human histocompatibility leukocyte antigen (HLA) molecules (HLA-A1 and B8), with clonal frequencies of one CTL per 10(-5) to 10(-6) splenic lymphocytes. Our data indicate that lymphoid organs may represent a major reservoir for in vivo activated HIV-specific CTL. Furthermore, the carboxyl-terminal domain of NEF was found to be conserved among several HIV strains. Therefore, our finding is of interest for further HIV vaccines development.
Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre Hôpitalier Universitaire Pitié-Salpétrière, Paris, France.
F
F
Hadida
A
A
Parrot
M P
MP
Kieny
B
B
Sadat-Sowti
C
C
Mayaud
P
P
Debre
B
B
Autran
D000595:Amino Acid Sequence; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D000939:Epitopes; D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef; D006680:HLA Antigens; D009842:Oligopeptides; D054311:nef Gene Products, Human Immunodeficiency Virus