Mhc-independent presentation of mycobacteria to human t cells

J. Holoshitz, N. C. Romzek, Y. Jia, L. Wagner, L. M. Vila, S. J. Chen, J. M. Wilson, D. R. Karp

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The majority of human peripheral T cells express antigen receptors using the VT9 and Vj2 gene products. Cells of this subset have been previously shown to uniformly recognize mycobacteria regardless of their V-(D)-J junctional sequences In an MHC-unrestrlcted manner. This reactivity superficially resembles activation of aß cells by bacterial superantigens, which are thought to be presented by monomorphlc regions of MHC class II molecules. It Is not known whether presentation of the mycobacterial antigen to V79/Vj2 T cells Is also mediated by class II MHC molecules. In order to examine the similarity between presentation of bacterial superantigens to T cells and the presentation of mycobacteria to yô T cells we have studied the role of class II MHC molecules In presentation of the mycobacterial antigen AP-MT to Vt9/Vj2 clones. Activation of T cells by AP-MT required direct contact with antigen presenting cells, Indicating that an Interaction with cell surface molecules on antigen presenting cells is required. Class II MHC molecules were neither sufficient nor necessary for effective presentation of AP-MT to the 75 T cells, as transfectants expressing class II MHC molecules were unable to present, whereas cell lines lacking expression of MHC class II molecules could present this mycobacterial antigen. Unlike presentation of staphylococcal enterotoxlns to aß T cells, which could be mediated by class II transfectants and was significantly augmented by co-expression of Intercellular adhesion molecule (ICAM)-1, presentation of AP-MT to T cells could not be enhanced by co-expression of class II and ICAM-1 molecules. Based on these results and our previous observation that presentation of AP-MT Is Independent of class I MHC molecules, we conclude that presentation of mycobacteria to human Vt9/Vj2 cells can be mediated by non-MHC cell surface molecules. These results Indicate that despite apparent similarities, recognition of mycobacteria by Vt9/Vj2 cells and activation of aß T cells by bacterial superantigens Involve distinct presentation mechanisms. The majority of human peripheral T cells express antigen receptors using the VT9 and Vj2 gene products. Cells of this subset have been previously shown to uniformly recognize mycobacteria regardless of their V-(D)-J junctional sequences In an MHC-unrestrlcted manner. This reactivity superficially resembles activation of aß cells by bacterial superantigens, which are thought to be presented by monomorphlc regions of MHC class II molecules. It Is not known whether presentation of the mycobacterial antigen to V79/Vj2 T cells Is also mediated by class II MHC molecules. In order to examine the similarity between presentation of bacterial superantigens to T cells and the presentation of mycobacteria to yô T cells we have studied the role of class II MHC molecules In presentation of the mycobacterial antigen AP-MT to Vt9/Vj2 clones. Activation of T cells by AP-MT required direct contact with antigen presenting cells, Indicating that an Interaction with cell surface molecules on antigen presenting cells is required. Class II MHC molecules were neither sufficient nor necessary for effective presentation of AP-MT to the 75 T cells, as transfectants expressing class II MHC molecules were unable to present, whereas cell lines lacking expression of MHC class II molecules could present this mycobacterial antigen. Unlike presentation of staphylococcal enterotoxlns to aß T cells, which could be mediated by class II transfectants and was significantly augmented by co-expression of Intercellular adhesion molecule (ICAM)-1, presentation of AP-MT to T cells could not be enhanced by co-expression of class II and ICAM-1 molecules. Based on these results and our previous observation that presentation of AP-MT Is Independent of class I MHC molecules, we conclude that presentation of mycobacteria to human Vt9/Vj2 cells can be mediated by non-MHC cell surface molecules. These results Indicate that despite apparent similarities, recognition of mycobacteria by Vt9/Vj2 cells and activation of aß T cells by bacterial superantigens Involve distinct presentation mechanisms.

Original languageEnglish (US)
Pages (from-to)1437-1443
Number of pages7
JournalInternational Immunology
Volume5
Issue number11
DOIs
StatePublished - Nov 1993

Keywords

  • Cdna
  • Cell surface molecules
  • Icam-1
  • Superantigens
  • T cell receptor
  • Transfectants

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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