Identification of type-specific cytotoxic T lymphocyte responses to homologous viral proteins in laboratory workers accidentally infected with HIV-1.
Characterization of the cytotoxic T lymphocyte (CTL) response against HIV-1 has been limited by the use of target cells expressing viral proteins from laboratory isolates of HIV-1. This approach has favored identification of group-specific CTL responses and precluded assessment of the extent of type-specific CTL responses directed against HIV-1. Using cells expressing viral proteins from the HIV-1 IIIB strain, we performed a detailed characterization of HIV-1-specific CTL response in three laboratory workers accidentally infected with HIV-1 IIIB. Eight of the epitopes identified were group specific, lying in relatively conserved regions of Gag, reverse transcriptase, and envelope. Three type-specific epitopes were identified, two of them in highly variable regions of envelope. In longitudinal studies in one subject, seven different epitopes and five different restricting HLA class I alleles were identified, with a progressive increase in the number of CTL epitopes recognized by this subject over time. Our data demonstrate that type-specific CTL responses make up a significant proportion of the host cellular immune response against HIV-1 and that a broadening of epitope specificity may occur.
Sipsas
N V
NV
AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital, Charlestown 02129, USA.
Kalams
S A
SA
Trocha
A
A
He
S
S
Blattner
W A
WA
Walker
B D
BD
Johnson
R P
RP
D000062:Accidents, Occupational; D000595:Amino Acid Sequence; D002469:Cell Separation; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D017056:Medical Laboratory Personnel; D009784:Occupational Diseases / Q000276:immunology* / Q000821:virology*; D012191:Retroviridae Proteins / Q000276:immunology*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology* / Q000821:virology*
D000939:Epitopes; D015686:Gene Products, env; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D012191:Retroviridae Proteins; D054303:HIV Reverse Transcriptase