PMID- 18391752
OWN - NLM
STAT- MEDLINE
DCOM- 20080708
LR  - 20200930
IS  - 1525-4135 (Print)
IS  - 1525-4135 (Linking)
VI  - 48
IP  - 2
DP  - 2008 Jun 1
TI  - Role of cytotoxic T-lymphocyte-mediated immune selection in a dominant human 
      leukocyte antigen-B8-restricted cytotoxic T-lymphocyte epitope in Nef.
PG  - 133-41
LID - 10.1097/QAI.0b013e31816fdc4a [doi]
AB  - OBJECTIVES: To study the role of cytotoxic T-lymphocyte (CTL) escape for disease 
      progression in HIV-1 infection, we analyzed the CTL response to the dominant 
      human leukocyte antigen (HLA)-B8-restricted CTL epitope FLKEKGGL (FL8) in HIV-1 
      Nef. METHODS: HIV-1 nef genes derived from 56 patients were analyzed by 
      polymerase chain reaction (PCR)-based sequencing. T-cell responses against FL8 
      and mutated FL8 variants were detected by gamma-interferon (gamma-IFN) enzyme 
      linked immunospot (ELISPOT) assay. RESULTS: The longitudinal analysis of an 
      HIV-1-infected patient with good control of HIV-1 viremia for several years 
      demonstrated an association of rising viremia with the emergence of CTL escape 
      mutations within the HLA-B8-restricted Nef-specific CTL epitopes FLKEKGGL and 
      WPAIRERM. Analysis of nef genes in 56 HIV-1-infected patients demonstrated a 
      significant correlation between the occurrence of mutations in the FL8 epitope 
      and the presence of HLA-B8. The mutations within the FL8 epitope could decrease 
      CTL recognition; however, there was strong variation regarding the recognition of 
      viral variants between individual donors. The presence of FL8 mutations was 
      associated with lower CD4 cell counts and higher viral loads. CONCLUSIONS: Our 
      data demonstrate a strong CTL selection pressure on the immunodominant 
      HLA-B8-restricted CTL epitope FL8 in HIV-1 Nef. The association of FL8 mutations 
      with lower CD4 cell counts indicates an important role of CTL escape mutations 
      for disease progression.
FAU - Maurer, Katja
AU  - Maurer K
AD  - Department of Internal Medicine 3, University Erlangen-Nuremberg, Germany.
FAU - Harrer, Ellen G
AU  - Harrer EG
FAU - Goldwich, Andreas
AU  - Goldwich A
FAU - Eismann, Kathrin
AU  - Eismann K
FAU - Bergmann, Silke
AU  - Bergmann S
FAU - Schmitt-Haendle, Matthias
AU  - Schmitt-Haendle M
FAU - Spriewald, Bernd
AU  - Spriewald B
FAU - Mueller, Sandra M
AU  - Mueller SM
FAU - Harrer, Thomas
AU  - Harrer T
CN  - German Competence Network for HIV/AIDS
LA  - eng
SI  - GENBANK/EU015077
SI  - GENBANK/EU015080
SI  - GENBANK/EU370449
SI  - GENBANK/EU370450
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Acquir Immune Defic Syndr
JT  - Journal of acquired immune deficiency syndromes (1999)
JID - 100892005
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B8 Antigen)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (nef Gene Products, Human Immunodeficiency Virus)
RN  - 0 (nef protein, Human immunodeficiency virus 1)
SB  - IM
EIN - J Acquir Immune Defic Syndr. 2009 Mar 1;50(3):343
MH  - Acquired Immunodeficiency Syndrome/*immunology/virology
MH  - Base Sequence
MH  - CD4 Lymphocyte Count
MH  - *Epitopes, T-Lymphocyte
MH  - Female
MH  - HLA-B8 Antigen/analysis/*physiology
MH  - Humans
MH  - *Immunodominant Epitopes
MH  - Longitudinal Studies
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Mutation
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Viral Load
MH  - nef Gene Products, Human Immunodeficiency Virus/chemistry/*immunology
EDAT- 2008/04/09 09:00
MHDA- 2008/07/09 09:00
CRDT- 2008/04/09 09:00
PHST- 2008/04/09 09:00 [pubmed]
PHST- 2008/07/09 09:00 [medline]
PHST- 2008/04/09 09:00 [entrez]
AID - 10.1097/QAI.0b013e31816fdc4a [doi]
PST - ppublish
SO  - J Acquir Immune Defic Syndr. 2008 Jun 1;48(2):133-41. doi: 
      10.1097/QAI.0b013e31816fdc4a.