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Journal of Virology, August 2005, p. 9503-9514, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9503-9514.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Humoral Immune Response Recognizes a Complex Set of Epitopes on Human Papillomavirus Type 6 L1 Capsomers{dagger}

Johnnie J. Orozco,1,2,3 Joseph J. Carter,1* Laura A. Koutsky,4 and Denise A. Galloway1,5

Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024,1 Department of Bioengineering, University of Washington, Seattle, Washington 98195-7962,2 Medical Scientist Training Program, University of Washington, Seattle, Washington 98195-7470,3 Department of Epidemiology, University of Washington, Seattle, Washington 98195-7236,4 Department of Microbiology, University of Washington, Seattle, Washington 98195-72425

Received 21 December 2004/ Accepted 13 April 2005

Although epitope mapping has identified residues on the human papillomavirus (HPV) major capsid protein (L1) that are important for binding mouse monoclonal antibodies, epitopes recognized by human antibodies are not known. To map epitopes on HPV type 6 (HPV6) L1, surface-exposed loops were mutated to the corresponding sequence of HPV11 L1. HPV6 L1 capsomers had one to six regions mutated, including the BC, DE, EF, FG, and HI loops and the 139 C-terminal residues. After verifying proper conformation, hybrid capsomers were used in enzyme-linked immunosorbent assays with 36 HPV6-seropositive sera from women enrolled in a study of incident HPV infection. Twelve sera were HPV6 specific, while the remainder reacted with both HPV6 and HPV11 L1. By preadsorption studies, 6/11 of these sera were shown to be cross-reactive. Among the HPV6-specific sera there was no immunodominant epitope recognized by all sera. Six of the 12 sera recognized epitopes that contained residues from combinations of the BC, DE, and FG loops, one serum recognized an epitope that consisted partially of the C-terminal arm, and three sera recognized complex epitopes to which reactivity was eliminated by switching all five loops. Reactivity in two sera was not eliminated even with all six regions swapped. The patterns of epitope recognition did not change over time in women whose sera were examined 9 years after their first-seropositive visit.

* Corresponding author. Mailing address: Program in Cancer Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., C1-015, Seattle, WA 98109-1024. Phone: (206) 667-4507. Fax: (206) 667-5815. E-mail: jcarter{at}fhcrc.org.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, August 2005, p. 9503-9514, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9503-9514.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Day, P. M., Thompson, C. D., Buck, C. B., Pang, Y.-Y. S., Lowy, D. R., Schiller, J. T. (2007). Neutralization of Human Papillomavirus with Monoclonal Antibodies Reveals Different Mechanisms of Inhibition. J. Virol. 81: 8784-8792 [Abstract] [Full Text]  
  • Carter, J. J., Wipf, G. C., Madeleine, M. M., Schwartz, S. M., Koutsky, L. A., Galloway, D. A. (2006). Identification of human papillomavirus type 16 l1 surface loops required for neutralization by human sera.. J. Virol. 80: 4664-4672 [Abstract] [Full Text]  


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