PMID- 15592417
OWN - NLM
STAT- MEDLINE
DCOM- 20050105
LR  - 20230621
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 432
IP  - 7018
DP  - 2004 Dec 9
TI  - Dominant influence of HLA-B in mediating the potential co-evolution of HIV and 
      HLA.
PG  - 769-75
AB  - The extreme polymorphism in the human leukocyte antigen (HLA) class I region of 
      the human genome is suggested to provide an advantage in pathogen defence 
      mediated by CD8+ T cells. HLA class I molecules present pathogen-derived peptides 
      on the surface of infected cells for recognition by CD8+ T cells. However, the 
      relative contributions of HLA-A and -B alleles have not been evaluated. We 
      performed a comprehensive analysis of the class I restricted CD8+ T-cell 
      responses against human immunodeficiency virus (HIV-1), immune control of which 
      is dependent upon virus-specific CD8+ T-cell activity. In 375 HIV-1-infected 
      study subjects from southern Africa, a significantly greater number of CD8+ 
      T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). 
      Here we show that variation in viral set-point, in absolute CD4 count and, by 
      inference, in rate of disease progression in the cohort, is strongly associated 
      with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, 
      respectively). Moreover, substantially greater selection pressure is imposed on 
      HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). These data indicate 
      that the principal focus of HIV-specific activity is at the HLA-B locus. 
      Furthermore, HLA-B gene frequencies in the population are those likely to be most 
      influenced by HIV disease, consistent with the observation that B alleles evolve 
      more rapidly than A alleles. The dominant involvement of HLA-B in influencing HIV 
      disease outcome is of specific relevance to the direction of HIV research and to 
      vaccine design.
FAU - Kiepiela, Photini
AU  - Kiepiela P
AD  - HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University 
      of KwaZuluNatal, 719 Umbilo Road, Durban 4015, South Africa.
FAU - Leslie, Alasdair J
AU  - Leslie AJ
FAU - Honeyborne, Isobella
AU  - Honeyborne I
FAU - Ramduth, Danni
AU  - Ramduth D
FAU - Thobakgale, Christina
AU  - Thobakgale C
FAU - Chetty, Senica
AU  - Chetty S
FAU - Rathnavalu, Prinisha
AU  - Rathnavalu P
FAU - Moore, Corey
AU  - Moore C
FAU - Pfafferott, Katja J
AU  - Pfafferott KJ
FAU - Hilton, Louise
AU  - Hilton L
FAU - Zimbwa, Peter
AU  - Zimbwa P
FAU - Moore, Sarah
AU  - Moore S
FAU - Allen, Todd
AU  - Allen T
FAU - Brander, Christian
AU  - Brander C
FAU - Addo, Marylyn M
AU  - Addo MM
FAU - Altfeld, Marcus
AU  - Altfeld M
FAU - James, Ian
AU  - James I
FAU - Mallal, Simon
AU  - Mallal S
FAU - Bunce, Michael
AU  - Bunce M
FAU - Barber, Linda D
AU  - Barber LD
FAU - Szinger, James
AU  - Szinger J
FAU - Day, Cheryl
AU  - Day C
FAU - Klenerman, Paul
AU  - Klenerman P
FAU - Mullins, James
AU  - Mullins J
FAU - Korber, Bette
AU  - Korber B
FAU - Coovadia, Hoosen M
AU  - Coovadia HM
FAU - Walker, Bruce D
AU  - Walker BD
FAU - Goulder, Philip J R
AU  - Goulder PJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Gene Products, nef)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (nef Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Africa, Southern
MH  - *Biological Evolution
MH  - CD8-Positive T-Lymphocytes/cytology/immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Female
MH  - Gene Frequency
MH  - Gene Products, nef/chemistry
MH  - HIV Infections/*immunology/*virology
MH  - HIV-1/genetics/*immunology/*physiology
MH  - HLA-A Antigens/genetics/immunology
MH  - HLA-B Antigens/genetics/*immunology
MH  - Humans
MH  - Infant
MH  - Male
MH  - Polymorphism, Genetic/genetics
MH  - Viral Load
MH  - nef Gene Products, Human Immunodeficiency Virus
EDAT- 2004/12/14 09:00
MHDA- 2005/01/06 09:00
CRDT- 2004/12/14 09:00
PHST- 2004/08/14 00:00 [received]
PHST- 2004/10/14 00:00 [accepted]
PHST- 2004/12/14 09:00 [pubmed]
PHST- 2005/01/06 09:00 [medline]
PHST- 2004/12/14 09:00 [entrez]
AID - nature03113 [pii]
AID - 10.1038/nature03113 [doi]
PST - ppublish
SO  - Nature. 2004 Dec 9;432(7018):769-75. doi: 10.1038/nature03113.