Journal of Virology, July 2007, p. 7725-7731, Vol. 81, No. 14
0022-538X/07/$08.00+0 doi:10.1128/JVI.00708-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Recognition of a Defined Region within p24 Gag by CD8+ T Cells during Primary Human Immunodeficiency Virus Type 1 Infection in Individuals Expressing Protective HLA Class I Alleles
Hendrik Streeck,1
Mathias Lichterfeld,1
Galit Alter,1
Angela Meier,1
Nickolas Teigen,1
Bader Yassine-Diab,2
Harlyn K. Sidhu,1
Susan Little,4
Anthony Kelleher,3
Jean-Pierre Routy,5
Eric S. Rosenberg,1
Rafick-Pierre Sekaly,2
Bruce D. Walker,1,6 and
Marcus Altfeld1*
Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital, and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129,1
Laboratoire d'Immunologie, Centre de Recherche du CHUM, Montreal, Quebec, Canada,2
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Darlinghurst, Australia,3
Department of Medicine, University of California, San Diego, San Diego, California 92093,4
McGill University, Division of Hematology and Immunodeficiency Service, Royal Victoria Hospital, Montreal, Quebec, Canada,5
Howard Hughes Medical Institute, Chevy Chase, Maryland 208156
Received 3 April 2007/
Accepted 2 May 2007
Human immunodeficiency virus type 1 (HIV-1)-specific immune responses during primary HIV-1 infection appear to play a critical role in determining the ultimate speed of disease progression, but little is known about the specificity of the initial HIV-1-specific CD8+ T-cell responses in individuals expressing protective HLA class I alleles. Here we compared HIV-1-specific T-cell responses between subjects expressing the protective allele HLA-B27 or -B57 and subjects expressing nonprotective HLA alleles using a cohort of over 290 subjects identified during primary HIV-1 infection. CD8+ T cells of individuals expressing HLA-B27 or -B57 targeted a defined region within HIV-1 p24 Gag (amino acids 240 to 272) early in infection, and responses against this region contributed over 35% to the total HIV-1-specific T-cell responses in these individuals. In contrast, this region was rarely recognized in individuals expressing HLA-B35, an HLA allele associated with rapid disease progression, or in subjects expressing neither HLA-B57/B27 nor HLA-B35 (P < 0.0001). The identification of this highly conserved region in p24 Gag targeted in primary infection specifically in individuals expressing HLA class I alleles associated with slower HIV-1 disease progression provides a rationale for vaccine design aimed at inducing responses to this region restricted by other, more common HLA class I alleles.
* Corresponding author. Mailing address: Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129. Phone: (617) 724-2461. Fax: (617) 724-8586. E-mail: maltfeld{at}partners.org
Published ahead of print on 9 May 2007.
Journal of Virology, July 2007, p. 7725-7731, Vol. 81, No. 14
0022-538X/07/$08.00+0 doi:10.1128/JVI.00708-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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Copyright © 2007 by the American Society for Microbiology. All rights reserved.