Chimeric β2m·h-2m3 single chain: a model for studying the functions of an mhc class i-b molecule

Academic Article


  • Major histocompatibilily complex (MHC) class I heavy chains non-covalcnily associate with β2-microglobulin (β2m) and peptide to form antigen complexes rccogniJ.ed by CD8+ cytotoxic T lymphocytes (CTL). The MHC cla.s.s I-b molecule H-2M3, which preferentially binds /V-formylated pcptidcs. is thought to play a specific role in the host immune response to prokaryotic pathogens. The function of individual class I antigens, however, is difficult to determine since a large number of class I loci are co-expressed in most tissues. To investigate the function of H-2M3, we have taken advantage of the finding that in the absence of $2\n, MHC class I antigens are not expressed at the cell surface. We have created a single chain p2m-M3 (SCβM3) chimcric MHC class I molecule in which β2m is covalently linked to the ami no terminus of the heavy chain. We hypothesize that, when expressed as ;i transgcnc in a βm knockout background, the single chain chimera will be the dominantly expressed MHC class I surface antigen. In vitro, SCβM3 is expressed at the surface of both βm positive and β2m negative cells. SCβM3 preferentially binds /V-formylaied pcptidcs and restricts a cytolytic response from CD8 CTL clones generated against wild type H-2M3 In β2m positive cells, SCβM3 is expressed on the surface associated with the chimeric β2m, and in β2m negative cells expression of transfccted SCβM3 docs not rescue endogenous class I surface expression. We have now created two independent founder iranssenic mice to be used for brccdinc SCβM3 -3?m''' transccnic lines.
  • Authors

    Author List

  • Levin JM; Rodgcrs JR; Howcll DD; Rich RR
  • Volume

  • 10
  • Issue

  • 6