Nized. All corresponding archived epitopes were different from those referenced from HXB2 and 4 were efficiently 94-09-7 presented while one was not: FPVTPQVPL (MHC 13.57)/FPVKPQVPV (MHC 30.21); FPVTPQVPLR (MHC 20,589)/FPVKPQVPVR (MHC 10,191); TPQVPLRPM (MHC 29.56)/KPQVPVRPM(MHC 11.17); RPMTYKAAV (MHC 5.53)/RPMTYKAAF(MHC 4.26); RPMTYKAAL (MHC 2.80)/RPMTYKAAF(MHC 4.26).G. The virus was subtype B. According to HLA alleles A*03:01, B*07:02 and B* 35:01, 13 epitopes corresponding to Gag 17?5, Gag 253?84, Nef 66?7 and Pol 325?55 could be evaluated. Most of them exhibited substitutions in the proviral DNA without variation in the MHC. One of them was no longer recognized: Gag 17?5; RLRPGGKKK (MHC 158.17)/RLRRPGGKKQ (MHC 14,882).Theoretical presentation of CTL epitopes in the sequenced parts of the archived proviral DNA. Differentpatterns were noted (Table 3). A. According to HLA allele A*03:01, the epitopes RT 33?3, RT 73?2, RT 93?01 of HXB2 can be presented with an MHC ranging from 45.58 to 367.82. The epitopes archived in the proviral DNA were identical. With HLA allele B*51:01, 2 epitopes of HXB2, RT 42?0 (EKEGKISKI) and RT 128?35 (TAFTIPSI) could be presented with an MHC of 36,931 and 2,032 respectively. The first archived epitope was unchanged while the second exhibited a substitution (TAFTIPSL) with an MHC switch from 2,032 to 11,857. B. We were able to investigate this patient’s viral RNA before the initiation of HAART and his proviral DNA at success. With HLA alleles 18204824 A*02:01, A*26:01, B*39:01 and B*40:01, 10 epitopes could be analyzed in Gag, Nef and Pol (RT). When we comparedToward a New Concept of HIV VaccineTable 2. Potential CTL reactivity against archived viral epitopes according to HLA I alleles: cross-reactivity to Lipo 5 peptides.PatientsViral subtype BHLA alleles HLA-A*03:Positions of the lipopeptides Pol 325?Target analyzed HXB2 ArchivedEpitopes AIFQSSMTK AIFQASMTK EIYKRWII EIYKRWII GGKKKYKLK GGKKKYKLK FPVTPQVPL FPVKPQVPV FPVTPQVPLR FPVKPQVPVR TPQVPLRPM KPQVPVRPM RPMTYKAAV RPMTYKAAF RPMTYKAAL RPMTYKAAF RLRPGGKKK RLRRPGGKKQMHC IC 50 12.04 20.24 257.38 257.38 31060.99 31060.99 13.57 30.21 20,589 10,191 29.56 11.17 5.53 4.26 2.80 4.26 158.17 14,ACBHLA-B*08:Gag1 253?HXB2 ArchivedGag2 17?HXB2 ArchivedECRF11_cpxHLA-B*07:Nef1 66?HXB2 ArchivedNef2 66?HXB2 ArchivedNef3 66?HXB2 ArchivedNef4 66?HXB2 ArchivedNef5 66?HXB2 ArchivedGBHLA-A*03:Gag 17?HXB2 ArchivedLipo 5 peptides are located in the viral genome and were designed from the HXB2 reference; according to the HLA alleles, we investigated the predicted reactivity against the corresponding epitopes or variants of these epitopes in archived proviral DNA. The MHC IC 50 values provide an estimation of the cross-reactivity between the epitope and the variant. For example, patient G with allele HLA-A*03:01 has archived a variant epitope that is poorly recognized. It is highly doubtful that the corresponding lipopeptide Gag 17?5 HXB2 vaccine lipopeptide will be 3PO chemical information useful for cross-stimulation. doi:10.1371/journal.pone.0069029.tthe HXB2 reference and viral RNA, 6 epitopes were strictly identical, 2 were mutated (with an increase in MHC) and 2 exhibited double populations at some codons and their corresponding residues. With HLA allele A*02:01, Gag p17 77?5 (SLYNTVATL) was present with an MHC of 476. The viral RNA presented the epitope SL[FY]NT[IV]STL with 4 different combinations and an MHC ranging from 178 to 759. Furthermore, with HLA allele B*40:01, the epitope Gag p17 92?01 IEIKDTKEAL was recogni.Nized. All corresponding archived epitopes were different from those referenced from HXB2 and 4 were efficiently presented while one was not: FPVTPQVPL (MHC 13.57)/FPVKPQVPV (MHC 30.21); FPVTPQVPLR (MHC 20,589)/FPVKPQVPVR (MHC 10,191); TPQVPLRPM (MHC 29.56)/KPQVPVRPM(MHC 11.17); RPMTYKAAV (MHC 5.53)/RPMTYKAAF(MHC 4.26); RPMTYKAAL (MHC 2.80)/RPMTYKAAF(MHC 4.26).G. The virus was subtype B. According to HLA alleles A*03:01, B*07:02 and B* 35:01, 13 epitopes corresponding to Gag 17?5, Gag 253?84, Nef 66?7 and Pol 325?55 could be evaluated. Most of them exhibited substitutions in the proviral DNA without variation in the MHC. One of them was no longer recognized: Gag 17?5; RLRPGGKKK (MHC 158.17)/RLRRPGGKKQ (MHC 14,882).Theoretical presentation of CTL epitopes in the sequenced parts of the archived proviral DNA. Differentpatterns were noted (Table 3). A. According to HLA allele A*03:01, the epitopes RT 33?3, RT 73?2, RT 93?01 of HXB2 can be presented with an MHC ranging from 45.58 to 367.82. The epitopes archived in the proviral DNA were identical. With HLA allele B*51:01, 2 epitopes of HXB2, RT 42?0 (EKEGKISKI) and RT 128?35 (TAFTIPSI) could be presented with an MHC of 36,931 and 2,032 respectively. The first archived epitope was unchanged while the second exhibited a substitution (TAFTIPSL) with an MHC switch from 2,032 to 11,857. B. We were able to investigate this patient’s viral RNA before the initiation of HAART and his proviral DNA at success. With HLA alleles 18204824 A*02:01, A*26:01, B*39:01 and B*40:01, 10 epitopes could be analyzed in Gag, Nef and Pol (RT). When we comparedToward a New Concept of HIV VaccineTable 2. Potential CTL reactivity against archived viral epitopes according to HLA I alleles: cross-reactivity to Lipo 5 peptides.PatientsViral subtype BHLA alleles HLA-A*03:Positions of the lipopeptides Pol 325?Target analyzed HXB2 ArchivedEpitopes AIFQSSMTK AIFQASMTK EIYKRWII EIYKRWII GGKKKYKLK GGKKKYKLK FPVTPQVPL FPVKPQVPV FPVTPQVPLR FPVKPQVPVR TPQVPLRPM KPQVPVRPM RPMTYKAAV RPMTYKAAF RPMTYKAAL RPMTYKAAF RLRPGGKKK RLRRPGGKKQMHC IC 50 12.04 20.24 257.38 257.38 31060.99 31060.99 13.57 30.21 20,589 10,191 29.56 11.17 5.53 4.26 2.80 4.26 158.17 14,ACBHLA-B*08:Gag1 253?HXB2 ArchivedGag2 17?HXB2 ArchivedECRF11_cpxHLA-B*07:Nef1 66?HXB2 ArchivedNef2 66?HXB2 ArchivedNef3 66?HXB2 ArchivedNef4 66?HXB2 ArchivedNef5 66?HXB2 ArchivedGBHLA-A*03:Gag 17?HXB2 ArchivedLipo 5 peptides are located in the viral genome and were designed from the HXB2 reference; according to the HLA alleles, we investigated the predicted reactivity against the corresponding epitopes or variants of these epitopes in archived proviral DNA. The MHC IC 50 values provide an estimation of the cross-reactivity between the epitope and the variant. For example, patient G with allele HLA-A*03:01 has archived a variant epitope that is poorly recognized. It is highly doubtful that the corresponding lipopeptide Gag 17?5 HXB2 vaccine lipopeptide will be useful for cross-stimulation. doi:10.1371/journal.pone.0069029.tthe HXB2 reference and viral RNA, 6 epitopes were strictly identical, 2 were mutated (with an increase in MHC) and 2 exhibited double populations at some codons and their corresponding residues. With HLA allele A*02:01, Gag p17 77?5 (SLYNTVATL) was present with an MHC of 476. The viral RNA presented the epitope SL[FY]NT[IV]STL with 4 different combinations and an MHC ranging from 178 to 759. Furthermore, with HLA allele B*40:01, the epitope Gag p17 92?01 IEIKDTKEAL was recogni.
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