T Cell Receptor Recognition Motifs Govern Immune Escape Patterns in Acute SIV Infection
Open Access
- 1 December 2004
- journal article
- research article
- Published by Elsevier BV in Immunity
- Vol. 21 (6), 793-803
- https://doi.org/10.1016/j.immuni.2004.10.010
Abstract
Escape from adaptive T cell immunity through transmutation of viral antigenic structure is a cardinal feature in the pathogenesis of SIV/HIV infection and a major obstacle to antiretroviral vaccine development. However, the molecular determinants of this phenomenon at the T cell receptor (TCR)-antigen interface are unknown. Here, we show that mutational escape is intimately linked to the structural configuration of constituent TCR clonotypes within virus-specific CD8+ T cell populations. Analysis of 3416 SIV-specific TCR sequences revealed that polyclonal T cell populations characterized by highly conserved TCRB CDR3 motifs were rendered ineffectual by single residue mutations in the cognate viral epitope. Conversely, diverse clonotypic repertoires without discernible motifs were not associated with viral escape. Thus, fundamental differences in the mode of antigen engagement direct the pattern of adaptive viral evolution. These findings have profound implications for the development of vaccines that elicit T cell immunity to combat pathogens with unstable genomes.Keywords
This publication has 57 references indexed in Scilit:
- Consequences of Cytotoxic T-Lymphocyte Escape: Common Escape Mutations in Simian Immunodeficiency Virus Are Poorly Recognized in Naïve HostsJournal of Virology, 2004
- The many important facets of T-cell repertoire diversityNature Reviews Immunology, 2004
- Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic feverNature Medicine, 2003
- Determinants of HIV-1 Mutational Escape From Cytotoxic T LymphocytesThe Journal of Experimental Medicine, 2003
- Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cellsBlood, 2003
- A Structural Basis for LCMV Immune Evasion: Subversion of H-2Db and H-2Kb Presentation of gp33 Revealed by Comparative Crystal Structure AnalysesImmunity, 2002
- Viral Persistence: HIV's Strategies of Immune System EvasionAnnual Review of Medicine, 2002
- Viral escape at the molecular level explained by quantitative T-cell receptor/peptide/MHC interactions and the crystal structure of a peptide/MHC complexJournal of Molecular Biology, 2000
- Increased peptide promiscuity provides a rationale for the lack of N regions in the neonatal T cell repertoireImmunity, 1995
- Structure and diversity of the T-cell receptor α chain in rhesus macaque and chimpanzeeHuman Immunology, 1995