Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infection.

  • Author(s): Draenert, Rika;
  • Le Gall, Sylvie;
  • Pfafferott, Katja J;
  • Leslie, Alasdair J;
  • Chetty, Polan;
  • Brander, Christian;
  • Holmes, Edward C;
  • Chang, Shih-Chung;
  • Feeney, Margaret E;
  • Addo, Marylyn M;
  • Ruiz, Lidia;
  • Ramduth, Danni;
  • Jeena, Prakash;
  • Altfeld, Marcus;
  • Thomas, Stephanie;
  • Tang, Yanhua;
  • Verrill, Cori L;
  • Dixon, Catherine;
  • Prado, Julia G;
  • Kiepiela, Photini;
  • Martinez-Picado, Javier;
  • Walker, Bruce D;
  • Goulder, Philip JR
  • et al.
Abstract

Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57-restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus-infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View