HIV-1 reverse transcriptase-specific CTL against conserved epitopes do not protect against progression to AIDS.
A small group of HIV-1-infected subjects who either do not progress to AIDS or progress only slowly have sustained HIV-1-specific CTL responses. It has been suggested that the specificities of these responses differ from the CTL responses of rapid progressors due to recognition of epitopes that are under structural or functional constraints. We have, in this respect, studied the CTL response to reverse transcriptase (RT) in long term survivors (LTS) and in HIV-1-infected individuals who progressed to AIDS within 3 to 6 yr. Both LTS and progressors displayed vigorous RT-specific CTL responses of comparable magnitude during the asymptomatic phase. From each individual at least two CTL lines were obtained from blood samples drawn at different time points during follow-up. A total of 19 CTL lines recognized nine different RT-derived epitopes. CTL obtained from progressors recognized epitopes with a similar degree of amino acid conservation as epitopes targeted by CTL from LTS. Furthermore, five of seven epitopes were recognized by both LTS and progressors. Moreover, one of the epitopes recognized by progressors contained the highly conserved YMDD motif that is essential for RT activity. In conclusion, our data imply that neither the magnitude nor the specificity of HIV-1-specific CTL against RT is a major cause of a more protracted course of disease.
van der Burg
S H
SH
Department of Immunohematology, Blood Bank, University Hospital, Leiden, The Netherlands.
Klein
M R
MR
Pontesilli
O
O
Holwerda
A M
AM
Drijfhout
J W
JW
Kast
W M
WM
Miedema
F
F
Melief
C J
CJ
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000276:immunology*; D000595:Amino Acid Sequence; D002460:Cell Line; D015331:Cohort Studies; D017124:Conserved Sequence / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D054303:HIV Reverse Transcriptase / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D054303:HIV Reverse Transcriptase