PMID- 21577229
OWN - NLM
STAT- MEDLINE
DCOM- 20120628
LR  - 20211020
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 90
IP  - 2
DP  - 2012 Feb
TI  - High-avidity, high-IFNgamma-producing CD8 T-cell responses following immune selection 
      during HIV-1 infection.
PG  - 224-34
LID - 10.1038/icb.2011.34 [doi]
AB  - HIV-1 mutations, which reduce or abolish CTL responses against virus-infected 
      cells, are frequently selected in acute and chronic HIV infection. Among 
      population HIV-1 sequences, immune selection is evident as human leukocyte 
      antigen (HLA) allele-associated substitutions of amino acids within or near CD8 
      T-cell epitopes. In these cases, the non-adapted epitope is susceptible to immune 
      recognition until an escape mutation renders the epitope less immunogenic. 
      However, several population-based studies have independently identified 
      HLA-associated viral changes, which lead to the formation of a new T-cell 
      epitope, suggesting that the immune responses that these variants or 
      'neo-epitopes' elicit provide an evolutionary advantage to the virus rather than 
      the host. Here, we examined the functional characteristics of eight CD8 T-cell 
      responses that result from viral adaptation in 125 HLA-genotyped individuals with 
      chronic HIV-1 infection. Neo-epitopes included well-characterized immunodominant 
      epitopes restricted by common HLA alleles, and in most cases the T-cell responses 
      against the neo-epitope showed significantly greater functional avidity and 
      higher IFNgamma production than T cells for non-adapted epitopes, but were not more 
      cytotoxic. Neo-epitope formation and emergence of cognate T-cell response 
      coincident with a rise in viral load was then observed in vivo in an acutely 
      infected individual. These findings show that HIV-1 adaptation not only abrogates 
      the immune recognition of early targeted epitopes, but may also increase immune 
      recognition to other epitopes, which elicit immunodominant but non-protective 
      T-cell responses. These data have implications for immunodominance associated 
      with polyvalent vaccines based on the diversity of chronic HIV-1 sequences.
FAU - Keane, Niamh M
AU  - Keane NM
AD  - Centre for Clinical Immunology and Biomedical Statistics, Institute for 
      Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, 
      Australia.
FAU - Roberts, Steven G
AU  - Roberts SG
FAU - Almeida, Coral-Ann M
AU  - Almeida CA
FAU - Krishnan, Tanya
AU  - Krishnan T
FAU - Chopra, Abha
AU  - Chopra A
FAU - Demaine, Emma
AU  - Demaine E
FAU - Laird, Rebecca
AU  - Laird R
FAU - Tschochner, Monika
AU  - Tschochner M
FAU - Carlson, Jonathan M
AU  - Carlson JM
FAU - Mallal, Simon
AU  - Mallal S
FAU - Heckerman, David
AU  - Heckerman D
FAU - James, Ian
AU  - James I
FAU - John, Mina
AU  - John M
LA  - eng
GR  - P30 AI110527/AI/NIAID NIH HHS/United States
GR  - R01 AI060460/AI/NIAID NIH HHS/United States
GR  - R01 AI060460-01/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110517
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA Antigens)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Epitopes, T-Lymphocyte/*genetics/immunology
MH  - HIV Infections/*immunology/virology
MH  - HIV-1/genetics/*immunology/pathogenicity
MH  - HLA Antigens/genetics/immunology
MH  - Humans
MH  - Interferon-gamma/*metabolism
MH  - Lymphocyte Activation
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Viral Load
PMC - PMC3173576
MID - NIHMS285249
EDAT- 2011/05/18 06:00
MHDA- 2012/06/29 06:00
PMCR- 2012/08/01
CRDT- 2011/05/18 06:00
PHST- 2011/05/18 06:00 [entrez]
PHST- 2011/05/18 06:00 [pubmed]
PHST- 2012/06/29 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - icb201134 [pii]
AID - 10.1038/icb.2011.34 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2012 Feb;90(2):224-34. doi: 10.1038/icb.2011.34. Epub 2011 May 
      17.