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Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope.

Authors :
Iversen AK
Stewart-Jones G
Learn GH
Christie N
Sylvester-Hviid C
Armitage AE
Kaul R
Beattie T
Lee JK
Li Y
Chotiyarnwong P
Dong T
Xu X
Luscher MA
MacDonald K
Ullum H
Klarlund-Pedersen B
Skinhøj P
Fugger L
Buus S
Mullins JI
Jones EY
van der Merwe PA
McMichael AJ
Source :
Nature immunology [Nat Immunol] 2006 Feb; Vol. 7 (2), pp. 179-89. Date of Electronic Publication: 2006 Jan 01.
Publication Year :
2006

Abstract

Cytotoxic T lymphocytes (CTLs) are critical for the control of human immunodeficiency virus, but containment of virus replication can be undermined by mutations in CTL epitopes that lead to virus escape. We analyzed the evolution in vivo of an immunodominant, HLA-A2-restricted CTL epitope and found two principal, diametrically opposed evolutionary pathways that exclusively affect T cell-receptor contact residues. One pathway was characterized by acquisition of CTL escape mutations and the other by selection for wild-type amino acids. The pattern of CTL responses to epitope variants shaped which variant(s) prevailed in the virus population. The pathways notably influenced the amount of plasma virus, as patients with efficient CTL selection had lower plasma viral loads than did patients without efficient selection. Thus, viral escape from CTL responses does not necessarily correlate with disease progression.

Details

Language :
English
ISSN :
1529-2908
Volume :
7
Issue :
2
Database :
MEDLINE
Journal :
Nature immunology
Publication Type :
Academic Journal
Accession number :
16388312
Full Text :
https://doi.org/10.1038/ni1298