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Journal of Virology, December 1999, p. 10191-10198, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Efficient Processing of the Immunodominant, HLA-A*0201-Restricted Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitope despite Multiple Variations in the Epitope Flanking Sequences

Christian Brander,1,* Otto O. Yang,1 Norman G. Jones,1 Yun Lee,1 Philip Goulder,1 R. Paul Johnson,1,2 Alicja Trocha,1 David Colbert,3 Christine Hay,1 Susan Buchbinder,3 Cornelia C. Bergmann,4 Hans J. Zweerink,5 Steven Wolinsky,6 William A. Blattner,7 Spyros A. Kalams,1 and Bruce D. Walker1

AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 021141; New England Regional Primate Center, Harvard Medical School, Southborough, Massachusetts 017722; HIV Research Section, Department of Public Health, San Francisco, California 941023; University of Southern California School of Medicine, Los Angeles, California 900334; Department of Inflammation and Rheumatology, Merck Research Laboratories, Rahway, New Jersey 070655; Department of Medicine, Northwestern University Medical School, Chicago, Illinois 606116; and Division of Geographic Medicine, University of Maryland, Baltimore, Maryland 212017

Received 26 April 1999/Accepted 29 August 1999

Immune escape from cytotoxic T-lymphocyte (CTL) responses has been shown to occur not only by changes within the targeted epitope but also by changes in the flanking sequences which interfere with the processing of the immunogenic peptide. However, the frequency of such an escape mechanism has not been determined. To investigate whether naturally occurring variations in the flanking sequences of an immunodominant human immunodeficiency virus type 1 (HIV-1) Gag CTL epitope prevent antigen processing, cells infected with HIV-1 or vaccinia virus constructs encoding different patient-derived Gag sequences were tested for recognition by HLA-A*0201-restricted, p17-specific CTL. We found that the immunodominant p17 epitope (SL9) and its variants were efficiently processed from minigene expressing vectors and from six HIV-1 Gag variants expressed by recombinant vaccinia virus constructs. Furthermore, SL9-specific CTL clones derived from multiple donors efficiently inhibited virus replication when added to HLA-A*0201-bearing cells infected with primary or laboratory-adapted strains of virus, despite the variability in the SL9 flanking sequences. These data suggest that escape from this immunodominant CTL response is not frequently accomplished by changes in the epitope flanking sequences.

* Corresponding author. Mailing address: AIDS Research Center, Massachusetts General Hospital-East, 149 13th St., Charlestown, MA 02129. Phone: (617) 724-5789. Fax: (617) 726-5411. E-mail: brander{at}helix.mgh.harvard.edu.

Journal of Virology, December 1999, p. 10191-10198, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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