Role of conserved regions of class I MHC molecules in the activation of CD8+ cytotoxic T lymphocytes by peptide and purified cell-free class I molecules

Toshiyuki Takeshita, Steven Kozlowski, Richard D. England, Richard Brower, Jonathan Schneck, Hidemi Takahashi, Charles Delisl, David H. Margulies, Jay A. Berzofsky

Research output: Contribution to journalArticle

Abstract

To analyze the molecular interactions involved in CD8+ cytotoxic T lymphocyte (CTL) recognition quantitatively, we developed a cell-free antigen presenting system. Genetically engineered soluble H-2Dd molecules coated on plastic microtiter plates could present HIV envelope peptide to an antigen-specific CTL clone, Inducing it to produce IFN-γ in the absence of accessory cells and their accessory or co-stimulatory molecules. The peptide-MHC complexes were functionally stable for over 24 h. The magnitude of T cell activation was dependent on the concentrations of both class I MHC molecule and the peptide, but was more sensitive to the concentration of the MHC molecule than to that of peptide. This result suggests that one MHC molecule can play more than one role in activating the CTL. One such role is the interaction between CD8 and a conserved region of class I MHC, as suggested by the finding that holding the total MHC concentration constant with an irrelevant class I MHC molecule (H-2Kb engineered to have the same a3 domain as H-2Dd) made the T cell response less sensitive to the change in concentration of the relevant MHC molecule (H-2Dd). The irrelevant class I MHC molecule (H-2Kb), unable to present this peptide by itself, augmented the T cell response at lower concentrations of peptide. These results suggest that the conserved α3 domain of the class I MHC heavy chain as well as polymorphic regions play an important role in T cell activation and that T cell interaction with MHC molecules not presenting peptide can still augment the response.

Original languageEnglish (US)
Pages (from-to)1129-1138
Number of pages10
JournalInternational Immunology
Volume5
Issue number9
DOIs
StatePublished - Sep 1993

Keywords

  • CD8+
  • Conserved regions
  • Cytotoxic T lymphocyte
  • MHC

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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