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Loss of HIV-1-derived cytotoxic T lymphocyte epitopes restricted by protective HLA-B alleles during the HIV-1 epidemic

Schellens, Ingrid M.M.a,*; Navis, Marjonb,*; van Deutekom, Hanneke W.M.c,e; Boeser-Nunnink, Brigitteb; Berkhout, Bend; Kootstra, Neeltjeb; Miedema, Franka; Keşmir, Canc,e; Schuitemaker, Hannekeb; van Baarle, Debbiea,f; Borghans, José A.M.a

doi: 10.1097/QAD.0b013e32834981b3
Basic Science

Objective and design: HIV-1 is known to adapt to the human immune system, leading to accumulation of escape mutations during the course of infection within an individual. Cross-sectional studies have shown an inverse correlation between the prevalence of human leukocyte antigen (HLA) alleles in a population and the number of cytotoxic T lymphocyte (CTL) escape mutations in epitopes restricted by those HLA alleles. Recently, it was demonstrated that at a population level HIV-1 is adapting to the humoral immune response, which is reflected in an increase in resistance to neutralizing antibodies over time. Here we investigated whether adaptations to cellular immunity have also accumulated during the epidemic.

Methods: We compared the number of CTL epitopes in HIV-1 strains isolated from individuals who seroconverted at the beginning of the HIV-1 epidemic and from individuals who seroconverted in recent calendar time.

Results: The number of CTL epitopes in HIV-1 variants restricted by the most common HLA alleles in the population did not change significantly during the epidemic. In contrast, we found a significant loss of CTL epitopes restricted by HLA-B alleles associated with a low relative hazard of HIV-1 disease progression during the epidemic. Such a loss was not observed for CTL epitopes restricted by HLA-A alleles.

Conclusion: Despite the large degree of HLA polymorphism, HIV-1 has accumulated adaptations to CTL responses within 20 years of the epidemic. The fact that such adaptations are driven by the HLA-B molecules that provide best protection against HIV-1 disease progression has important implications for our understanding of HIV evolution.

aDepartment of Immunology, University Medical Center Utrecht, Utrecht

bDepartment of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam

cDepartment of Theoretical Biology/Bioinformatics, Utrecht University, Utrecht

dLaboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, Amsterdam

eAcademic Biomedical Centre, Utrecht University

fDepartment of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.

*Ingrid M.M. Schellens and Marjon Navis contributed equally to this article.

Correspondence to José Borghans, Department of Immunology, KC02-085.2, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands. Tel: +31 88 7554275; fax: +31 88 7554305; e-mail: j.borghans@umcutrecht.nl

Received 17 February, 2011

Revised 23 May, 2011

Accepted 3 June, 2011

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© 2011 Lippincott Williams & Wilkins, Inc.