Construction of novel class I histocompatibility antigens by interspecies exon shuffling

V. H. Engelhard, J. R. Yannelli, G. A. Evans, S. F. Walk, M. J. Holterman

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Human and mouse class I histocompatibility antigens share considerable structural homology at both the protein and DNA sequence level. This homology has allowed the production of hybrid class I molecules by the reciprocal exchange of DNA sequences corresponding to equivalent domains of HLA-B7 and either H-2L(d) or H-2D(d). It is shown that these genes give rise to protein products that are stably expressed on the surface of murine L cells after DNA-mediated gene transfer. These proteins express only those monoclonal antibody-defined H-2 determinants that are expected based on their genetic construction. The molecules have allowed the localization of a number of polymorphic and monomorphic HLA-specific epitopes. In all but one case, expression of an epitope on a domain does not appear to be influenced by the replacement of adjacent human domains with their murine equivalents, suggesting a considerable degree of structural independence of the domains. Cells expressing the hybrid molecules have also been tested as targets for a panel of HLA-B7-specific cytotoxic T cell clones. The results show that the polymorphic determinants recognized by these clones map to the α1 and α2 domains of the HLA-B7 molecule. No evidence for an influence of species-related amino acid sequence differences in the third extracellular domain on T cell recognition was seen. The results are discussed in light of the proposed domain structure of the class I proteins and the potential use of such molecules for further functional studies.

Original languageEnglish
Pages (from-to)4218-4225
Number of pages8
JournalJournal of Immunology
Volume134
Issue number6
StatePublished - 1985

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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