Cutting edge: single-chain trimers of MHC class I molecules form stable structures that potently stimulate antigen-specific T cells and B cells

J Immunol. 2002 Apr 1;168(7):3145-9. doi: 10.4049/jimmunol.168.7.3145.

Abstract

We report in this work the expression and characterization of class I molecules expressed as single-chain trimers consisting of an antigenic peptide-spacer-beta(2)-microglobulin-spacer H chain. Our results indicate that these single-chain constructs assemble efficiently, maintain their covalent structure, and are unusually stable at the cell surface. Consequently, these constructs are at least 1000-fold less accessible to exogenous peptide than class I molecules loaded with endogenous peptides, and they are potent simulators of peptide-specific CTL and Abs. Our combined findings suggest that single-chain trimers may have applications as DNA vaccines against virus infection or tumors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Egg Proteins / chemistry
  • Egg Proteins / genetics
  • Egg Proteins / immunology
  • Egg Proteins / physiology
  • Epitopes, B-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Genetic Vectors / chemical synthesis
  • Genetic Vectors / immunology
  • Genetic Vectors / physiology
  • H-2 Antigens / chemistry
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology
  • H-2 Antigens / physiology
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / physiology*
  • L Cells
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / chemistry
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Ovalbumin / physiology
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / physiology*
  • Structure-Activity Relationship
  • T-Lymphocytes / immunology*
  • beta 2-Microglobulin / chemical synthesis
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / physiology

Substances

  • Egg Proteins
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Histocompatibility Antigens Class I
  • OVA-8
  • Peptide Fragments
  • beta 2-Microglobulin
  • Ovalbumin