Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection

نویسندگان

  • Akihisa Shimizu
  • Ai Kawana-Tachikawa
  • Atsushi Yamagata
  • Chungyong Han
  • Dayong Zhu
  • Yusuke Sato
  • Hitomi Nakamura
  • Tomohiko Koibuchi
  • Jonathan Carlson
  • Eric Martin
  • Chanson J. Brumme
  • Yi Shi
  • George F. Gao
  • Zabrina L. Brumme
  • Shuya Fukai
  • Aikichi Iwamoto
چکیده

We investigated the crystal structure of an HLA-A*2402-restricted CTL epitope in the HIV-1 nef gene (Nef134-10) before (pHLA) or after TCR docking. The wild type epitope and two escape mutants were included in the study. Y135F was an early-appearing major mutation, while F139L was a late-appearing mutation which was selected in the patients without Y135F. F139 was an eminent feature of the Nef134-10 epitope. Wild type-specific TCR was less fit to F139L mutant suggesting that F139L is an escape from the CTL against the wild type epitope. Although Y135F mutation disrupted the hydrogen bond to HLA-A*2402 His70, newly formed hydrogen bond between T138 and His70 kept the conformation of the epitope in the reconstituted pMHC. TCR from Y135F- or dually-specific CTL had unique mode of binding to the mutant epitope. Y135F has been reported as a processing mutant but CTL carrying structurally adequate TCR can be found in the patients.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Longitudinal Analysis of T Cell Receptor ( TCR ) Gene Usage by Human lmmunodeficiency Virus 1 Envelope - specific Cytotoxic T Lymphocyte Clones Reveals a Limited TCR

Human immunodeficiency virus 1 (HW-1) infection is associated with a vigorous cellular immune response that allows detection of cytotoxic T lymphocyte (CTL) activity using fleshly isolated peripheral blood mononudear cells (PBMC). Although restricting class I antigens and epitopes recognized by HIV-l-specific CTL have been defined, the effector cells mediating this vigorous response have been c...

متن کامل

Longitudinal Analysis of T Cell Receptor ( TCR ) Gene Usage by Human lmmunodeficiency Virus 1 Envelope - specific Cytotoxic T Lymphocyte Clones

Human immunodeficiency virus 1 (HW-1) infection is associated with a vigorous cellular immune response that allows detection of cytotoxic T lymphocyte (CTL) activity using fleshly isolated peripheral blood mononudear cells (PBMC). Although restricting class I antigens and epitopes recognized by HIV-l-specific CTL have been defined, the effector cells mediating this vigorous response have been c...

متن کامل

Persistent HIV-1-specific CTL clonal expansion despite high viral burden post in utero HIV-1 infection.

To address the issue of clonal exhaustion in humans, we monitored HLA class I-restricted, epitope-specific CTL responses in an in utero HIV-1-infected infant from 3 mo through 5 years of age. Serial functional CTL precursor assays demonstrated persistent, vigorous, and broadly directed HIV-1 specific CTL activity with a dominant response against an epitope in HIV-1 Gag-p17 (SLYNTVATL, aa 77-85)...

متن کامل

A viral CTL escape mutation leading to immunoglobulin-like transcript 4–mediated functional inhibition of myelomonocytic cells

Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide-major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the...

متن کامل

Portable flanking sequences modulate CTL epitope processing.

Peptide presentation is critical for immune recognition of pathogen-infected cells by CD8+ T lymphocytes. Although a limited number of immunodominant peptide epitopes are consistently observed in diseases such as HIV-1 infection, the relationship between immunodominance and antigen processing in humans is largely unknown. Here, we have demonstrated that endogenous processing and presentation of...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2013