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- Variants ILK(D/E)PVHGV are A/B clade specific.
- ELISPOT was used to study CTL responses to a panel of 54 predefined HIV-1 epitopes in 91 HIV-1-exposed, persistently seronegative (HEPS) and 87 HIV-1-infected female Nairobi sex workers.
- Responses in HEPS women tended to be lower, and focused on different epitopes with HLA presenting molecules that have previously been associated with reduced risk of infection, and there was a shift in the response in the HEPS women upon late seroconversion to epitopes recognized by the HIV-1 infected women.
- 43/91 HEPS women had CD8+ responses and detection of HIV-1-specific CTL in HEPS women increased with the duration of viral exposure.
- Among HLA-A2 women, 7/10 HEPS and 14/26 HIV-1 infected women recognized this epitope, and ILK(D/E)PVHGV tended to be more reactive in HEPS women, SL(F/Y)NTVATL in infected women.
- The dominant response to this HLA allele was to this epitope in all 7/10 HEPS cases but in only 5 of the 14/26 HIV-1 infected women.
- Four epitopes were considered to be ``resistant epitopes'', as they were preferentially reactive in HEPS women and so may confer resistance, and these were found in three different proteins: A2 ILK(D/E)PVHGV in RT, A*6802 DTVLEDINL in Protease, B14 DLN(M/T)LN(I/V)V in p24 and B18 FRDYVDRF(Y/F)K also in p24.
- Differences in epitope specificity were only seen for responses restricted by class I HLA alleles A2, A24, A*6802, B14, and B18, previously shown to be associated with resistance to HIV-1 in this cohort.
- Subject ML 1250 had an A2 response to ILK(D/E)PVHGV prior to seroconversion, which switched to SL(F/Y)NTVATL post-seroconversion.
- Subject ML 1760 had an A2 response to ILK(D/E)PVHGV prior to seroconversion, and gained responses to epitopes A2 SL(F/Y)NTVATL and B27 KRWII(L/M)GLNK post-seroconversion.
References
Kaul2001a
R. Kaul, T. Dong, F. A. Plummer, J. Kimani, T. Rostron, P. Kiama, E. Njagi, E. Irungu, B. Farah, J. Oyugi, R. Chakraborty, K. S. MacDonald, J. J. Bwayo, A. McMichael, and S. L. Rowland-Jones. CD8(+) lymphocytes respond to different HIV epitopes in seronegative and infected subjects. J. Clin. Invest., 107(10):1303-10, May 2001. URL: http://www.jci.org/cgi/content/full/107/10/1303. PubMed ID: 11375420.
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