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


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; (2006) Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope. Nature immunology, 7 (2). pp. 179-89. ISSN 1529-2908 DOI: https://doi.org/10.1038/ni1298

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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.

Item Type: Article
Faculty and Department: Faculty of Public Health and Policy > Dept of Global Health and Development
Research Centre: Social and Mathematical Epidemiology (SaME)
SaME Modelling & Economics
PubMed ID: 16388312
Web of Science ID: 234801700019
URI: http://researchonline.lshtm.ac.uk/id/eprint/40609

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