The lifespan of major histocompatibility complex class I/peptide complexes determines the efficiency of cytotoxic T-lymphocyte responses

Immunology. 1999 Mar;96(3):411-5. doi: 10.1046/j.1365-2567.1999.00707.x.

Abstract

Major histocompatibility complex (MHC)/peptide association and stability are determined by specific amino acid interactions between peptide antigens and the MHC groove, and are regarded as a critical feature in ensuring efficient monitoring by T cells. In this investigation we examined the relationship between MHC/peptide stability and the immunostimulatory capacity of MHC/peptide complexes. For this purpose we compared synthetic peptide analogues derived from the immunodominant HLA-A11-presented IVTDFSVIK (IVT) epitope, for their capacity to reactivate IVT-specific memory cytotoxic T-lymphocyte (CTL) responses. The analogues differentiated from the wild-type epitope by single amino acid substitution at position 2. All peptides showed similar affinity for HLA-A11 molecules and were recognized by IVT-specific CTL clones, but induced HLA-A11 complexes at the cell surface with different lifespan. This model offered the possibility of comparing the capacity of an immunogenic epitope to stimulate a unique population of T-cell precursors depending on the lifespan of its presentation at the cell surface. We demonstrated that stable HLA-A11/peptide complexes efficiently stimulate IVT-specific CTL responses, while HLA-A11/peptide complexes with short lifespan do not. The precise identification of the role of amino acid residues in the formation of stable MHC/peptide complexes may be relevant for the design of wild-type-derived epitopes with high immunogenicity. These analogues may have important applications in the immunotherapy of infectious diseases and immunogenic tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cell Line
  • Cytotoxicity, Immunologic
  • Epitopes / immunology
  • Epstein-Barr Virus Nuclear Antigens / immunology
  • HLA-A Antigens / immunology
  • HLA-A11 Antigen
  • Half-Life
  • Herpesvirus 4, Human / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunologic Memory
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Epitopes
  • Epstein-Barr Virus Nuclear Antigens
  • HLA-A Antigens
  • HLA-A11 Antigen
  • Histocompatibility Antigens Class I
  • Peptide Fragments