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Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope.
- 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.
- Subjects :
- Adult
Amino Acid Sequence
Crystallography, X-Ray
Evolution, Molecular
Female
Gene Products, gag chemistry
Gene Products, gag genetics
Gene Products, gag immunology
Genetic Variation
HIV Antigens metabolism
HIV Infections immunology
HIV Infections virology
HLA-A2 Antigen chemistry
HLA-A2 Antigen metabolism
Humans
Immunodominant Epitopes genetics
Immunodominant Epitopes metabolism
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes
Mutation
Peptide Fragments chemistry
Peptide Fragments genetics
Peptide Fragments immunology
Phylogeny
Selection, Genetic
T-Lymphocytes, Cytotoxic immunology
Viremia immunology
Viremia virology
env Gene Products, Human Immunodeficiency Virus
HIV Antigens genetics
HIV-1 genetics
HIV-1 immunology
Receptors, Antigen, T-Cell metabolism
Subjects
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