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Journal of Virology, June 2000, p. 5679-5690, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Differential Narrow Focusing of Immunodominant Human Immunodeficiency Virus Gag-Specific Cytotoxic T-Lymphocyte Responses in Infected African and Caucasoid Adults and Children

Philip J. R. Goulder,1,2,* C. Brander,1 K. Annamalai,3 N. Mngqundaniso,3 U. Govender,3 Y. Tang,1 S. He,1 K. E. Hartman,1 C. A. O'Callaghan,4 G. S. Ogg,4 M. A. Altfeld,1 E. S. Rosenberg,1 H. Cao,1 S. A. Kalams,1 M. Hammond,5 M. Bunce,6 S. I. Pelton,7 S. A. Burchett,2 K. McIntosh,2 H. M. Coovadia,3 and B. D. Walker1

Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 021291; Division of Infectious Diseases, The Children's Hospital,2 and Section of Pediatric Infectious Diseases, Boston Medical Center,7 Boston, Massachusetts 02118; Department of Paediatrics, University of Natal,3 and Natal Blood Transfusion Service, Pinetown,5 Durban, South Africa; and MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU,4 and Oxford Transplant Centre, Churchill Hospital, Oxford OX3 7LJ,6 United Kingdom

Received 11 January 2000/Accepted 28 March 2000

Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of viral replication and in determining outcome in cases of human immunodeficiency virus type 1 (HIV-1) infection. Incorporation of important CTL epitope sequences into candidate vaccines is, therefore, vital. Most CTL studies have focused upon small numbers of adult Caucasoid subjects infected with clade-B virus, whereas the global epidemic is most severe in sub-Saharan African populations and predominantly involves clade-C infection in both adults and children. In this study, sensitive enzyme-linked immunospot (elispot) assays have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus. Cohorts evaluated included 44 B-clade-infected Caucasoid American and African American adults and children and 37 C-clade-infected African adults and children from Durban, South Africa. The results show that 3 out of 46 peptides spanning p17Gag and p24Gag sequences tested contain two-thirds of the dominant Gag-specific epitopes, irrespective of the clade, ethnicity, or age group studied. However, there were distinctive differences between the dominant responses made by Caucasoids and Africans. Dominant responses in Caucasoids were more often within p17Gag peptide residues 16 to 30 (38 versus 12%; P < 0.01), while p24Gag peptide residues 41 to 60 contained the dominant Gag epitope more often in the African subjects tested (39 versus 4%; P < 0.005). Within this 20-mer p24Gag, an epitope presented by both B42 and B81 is defined which represents the dominant Gag response in >30% of the total infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high immunogenicity is of significance to vaccine design.

* Corresponding author. Mailing address: Partners AIDS Research Center, Massachusetts General Hospital, 13th St., Bldg. 149, Rm. 5218, Charlestown, MA 02129. Phone: (617) 726-5787. Fax: (617) 726-5411. E-mail: goulder{at}helix.mgh.harvard.edu.

Journal of Virology, June 2000, p. 5679-5690, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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