Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype
Journal of Immunology, Volume 177, No. 7, Year 2006
Notification
URL copied to clipboard!
Description
HLA diversity is seen as a major challenge to CTL vaccines against HIV. One current approach focuses on "promiscuous" epitopes, presented by multiple HLA alleles from within the same HLA supertype. However, the effectiveness of such supertype vaccines depends upon the functional equivalence of CTL targeting a particular epitope, irrespective of the restricting HLA. In this study, we describe the promiscuous HIV-specific CTL epitopes presented by alleles within the B7 supertype. Substantial differences were observed in the ability of CTL to select for escape mutation when targeting the same epitope but restricted by different HLA. This observation was common to all six promiscuous B7 epitopes identified. Moreover, with one exception, there were no significant differences in the frequency, magnitude, or immunodominance of the CTL responses restricted by different HLA alleles to explain these discrepancies. This suggests that the unique peptide/MHC complexes generated by even closely related HLA induce CTL responses that are qualitatively different. This hypothesis is supported by additional differences observed between CTL targeting identical epitopes but restricted by different HLA: first, the occurrence of distinct, HLA-specific escape mutation; second, the recruitment of distinct TCR repertoires by particular peptide/MHC complexes; and, third, significant differences in the functional avidity of CTL. Taken together, these data indicate that significant functional differences exist between CTL targeting identical epitopes but restricted by different, albeit closely related HLA. These findings are of relevance to vaccine approaches that seek to exploit HLA supertypes to overcome the problem of HLA diversity. Copyright © 2006 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Leslie, Alasdair J.
United Kingdom, Oxford
Nuffield Department of Medicine
United Kingdom, Oxford
University of Oxford
Price, David Ashley
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Mkhize, Pamela
South Africa, Durban
University of Kwazulu-natal
Bishop, Karen S.
South Africa, Durban
University of Kwazulu-natal
Rathod, Almas
South Africa, Durban
University of Kwazulu-natal
Day, Cheryl Cheryl L.
South Africa, Durban
University of Kwazulu-natal
Crawford, Hayley
United Kingdom, Oxford
Nuffield Department of Medicine
Honeyborne, Isobella
United Kingdom, Oxford
Nuffield Department of Medicine
Asher, Tedi E.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Luzzi, Graz A.
United Kingdom, High Wycombe
Wycombe Hospital
Edwards, Anne R.
United Kingdom, Oxford
Radcliffe Infirmary
Rosseau, Christine M.
United States, Seattle
University of Washington School of Medicine
Mullins, James I.
United States, Seattle
University of Washington School of Medicine
Tudor-Williams, Gareth
United Kingdom, London
St Mary's Hospital
Novelli, Vas M.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Brander, Christian
United States, Boston
Massachusetts General Hospital
Douek, Daniel Cesar
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Kiepiela, Photini
South Africa, Durban
University of Kwazulu-natal
Walker, Bruce D.
United States, Boston
Massachusetts General Hospital
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
Nuffield Department of Medicine
South Africa, Durban
University of Kwazulu-natal
Statistics
Citations: 56
Authors: 20
Affiliations: 10
Identifiers
Doi:
10.4049/jimmunol.177.7.4699
ISSN:
00221767
Research Areas
Cancer
Infectious Diseases