PMID- 19542300
OWN - NLM
STAT- MEDLINE
DCOM- 20090930
LR  - 20240508
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 114
IP  - 8
DP  - 2009 Aug 20
TI  - Minor viral and host genetic polymorphisms can dramatically impact the biologic 
      outcome of an epitope-specific CD8 T-cell response.
PG  - 1553-62
LID - 10.1182/blood-2009-02-206193 [doi]
AB  - Human immunodeficiency virus-1 subtypes A and C differ in the highly conserved 
      Gag-TL9 epitope at a single amino acid position. Similarly, the TL9 presenting 
      human leukocyte antigen (HLA) class I molecules B42 and B81 differ only at 6 
      amino acid positions. Here, we addressed the influence of such minor viral and 
      host genetic variation on the TL9-specific CD8 T-cell response. The clonotypic 
      characteristics of CD8 T-cell populations elicited by subtype A or subtype C were 
      distinct, and these responses differed substantially with respect to the 
      recognition and selection of TL9 variants. Irrespective of the presenting HLA 
      class I molecule, CD8 T-cell responses elicited by subtype C exhibited largely 
      comparable TL9 variant cross-recognition properties, expressed T-cell receptors 
      that used almost exclusively the TRBV 12-3 gene, and selected for predictable 
      patterns of viral variation within TL9. In contrast, subtype A elicited 
      TL9-specific CD8 T-cell populations with completely different, more diverse TCRBV 
      genes and did not select for viral variants. Moreover, TL9 variant 
      cross-recognition properties were extensive in B81(+) subjects but limited in 
      B42(+) subjects. Thus, minor viral and host genetic polymorphisms can 
      dramatically alter the immunologic and virologic outcome of an epitope-specific 
      CD8 T-cell response.
FAU - Geldmacher, Christof
AU  - Geldmacher C
AD  - Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and 
      Infectious Diseases, NIH, Bethesda, MD, USA. geldmacher@lrz.uni-muenchen.de
FAU - Metzler, Ian S
AU  - Metzler IS
FAU - Tovanabutra, Sodsai
AU  - Tovanabutra S
FAU - Asher, Tedi E
AU  - Asher TE
FAU - Gostick, Emma
AU  - Gostick E
FAU - Ambrozak, David R
AU  - Ambrozak DR
FAU - Petrovas, Constantinos
AU  - Petrovas C
FAU - Schuetz, Alexandra
AU  - Schuetz A
FAU - Ngwenyama, Njabulo
AU  - Ngwenyama N
FAU - Kijak, Gustavo
AU  - Kijak G
FAU - Maboko, Leonard
AU  - Maboko L
FAU - Hoelscher, Michael
AU  - Hoelscher M
FAU - McCutchan, Francine
AU  - McCutchan F
FAU - Price, David A
AU  - Price DA
FAU - Douek, Daniel C
AU  - Douek DC
FAU - Koup, Richard A
AU  - Koup RA
LA  - eng
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090619
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA, Viral)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - DNA Mutational Analysis
MH  - DNA, Viral/analysis/genetics
MH  - Epitopes, T-Lymphocyte/*genetics/immunology
MH  - Female
MH  - HIV Infections/genetics/immunology
MH  - HIV-1/*genetics/*immunology
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Host-Pathogen Interactions/genetics/immunology
MH  - Humans
MH  - Polymorphism, Genetic/*physiology
MH  - Receptors, Antigen, T-Cell/genetics
MH  - Sequence Homology, Amino Acid
MH  - T-Cell Antigen Receptor Specificity/genetics/immunology
MH  - Viral Proteins/genetics/immunology
PMC - PMC2731637
EDAT- 2009/06/23 09:00
MHDA- 2009/10/01 06:00
PMCR- 2010/08/20
CRDT- 2009/06/23 09:00
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2009/10/01 06:00 [medline]
PHST- 2010/08/20 00:00 [pmc-release]
AID - S0006-4971(20)37181-0 [pii]
AID - 2009/206193 [pii]
AID - 10.1182/blood-2009-02-206193 [doi]
PST - ppublish
SO  - Blood. 2009 Aug 20;114(8):1553-62. doi: 10.1182/blood-2009-02-206193. Epub 2009 
      Jun 19.