11th International AIDS Conference Vancouver, British Columbia — July 7-12, 1996

Int Conf AIDS 1996 Jul 7-12; 11:211 (abstract no. Th.A.141)
Ishiko H, West K, Zeng W, Spaulding A, Ennis FA; Univ. of Mass. Med. Ctr., Div. of Infect. Dis., Worcester, MA. Fax: (508) 856-4890. E-mail: hishiko@ummed.edu.

OBJECTIVE: The purpose of our research is to define the CD8+ CTL responses to unique, autologous sequences on HIV-1 gp41 in comparison to the CD8+ CTL responses cross-reactive to prototype strains.

METHODS: 5' and 3' truncated gp41 RNA sequences of virus particles in the plasma of a patient were amplified by RT-nested PCR to cover the full length of gp41. These PCR products were subcloned and sequenced. Recombinant vaccinia viruses (rVac) were generated with these autologous gp41 fragments by homologous recombination. CD8+ CTLs were isolated with lytic activity against autologous B-LCL infected with rVac expressing prototype sequences (supplied by Dr. B. Moss) or autologous gp41 sequences.

RESULTS: Sequence Analysis - The gp41 sequences cloned from this patient's plasma in 1994 and 1995 were heterogeneous with 95% homology between amino acid sequences. One of these autologous clones has 45 amino acid mutations (13%) compared to REHTLV3. We generated five rVac. Two rVac have two thirds of the 5' autologous gp41 sequences, two rVac have two-thirds of the 3' autologous gp41 sequences, and one rVac has the full gp41 sequence. CD8+CTLs - We established five CTL lines that were gp41 specific; 4 recognized the unique autologous gp41 sequence and 1 also recognized prototype gp41. One of the autologous specific CTL lines has been analyzed and recognize overlapping sequences on both the 5' and 3' truncated autologous gp41 sequences. The only mutation in the overlap region that can explain the differences in recognition by this CD8+ CTL line is a G and S mutation at aa 640. This clone is HLA A23 restricted.

CONCLUSION: We speculate that the infected individual mounts CD8+ CTL responses to unique, autologous as well as to prototype, cross-reactive sequences. Only ten human CD8+ CTL epitopes on gp41 have been defined and all are cross-reactive because they were detected using a vaccinia recombinant virus that expresses prototype gp41. It is important to learn about these unique autologous CTL responses as part of understanding the interactions between this mutation-prone virus with the CD8+ CTL of infected individuals.

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ThA141

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