Expression and function of HLA-DR3 and DQ8 in transgenic mice lacking functional H2-M

G. Rajagopalan, M. K. Smart, S. Cheng, C. J. Krco, K. L. Johnson, Chella S. David

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

H2-M or HLA-DM are non-classical class II molecules encoded by the MHC and play an important role during antigen presentation. They catalyze exchange of CLIP (Class II-associated invariant chain peptide) or other low-affinity peptides bound to class II molecules for peptides capable of more efficient binding. The phenotype of mice lacking H2-M is determined by the allotype of the MHC dass II molecules expressed. In general, H2-M deficiency does not affect the surface expression of mature dass II molecules. The class II molecules in such cases predominantly contain CLIP in their peptide-binding groove. In some mice strains, H2-M deficiency results in defective CD4 + T-cell development accompanied by defective responses to conventional antigens and superantigens. Even though the HLA class II molecules show similar dependency for HLA-DM for presenting antigens in vitro, their interaction in vivo is not known. By using transgenic approach we show here that DQ8 and DR3 are expressed at normal levels in H2-M. defident mice and the CD4+ T-cell development is unaltered. However, the ability of DQ8 molecules to present peptide antigens is compromised in a H2-M-defident state. Presentation of exogenous bacterial superantigens by both DQ8 and DR3 is unaffected in H2-M-deficient mice. Unexpectedly, Staphylococcal Enterotoxin B-induced systemic IFN-γ production was significantly higher in H2-M-deficient DQ8/DR3 transgenic mice and these mice were susceptible to SEB-induced toxic shock at doses that are non-lethal to H2·M-sufficient counterparts.

Original languageEnglish (US)
Pages (from-to)149-161
Number of pages13
JournalTissue Antigens
Volume62
Issue number2
DOIs
StatePublished - Aug 1 2003

Keywords

  • Antigen presentation/processing
  • HLA
  • MHC
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Genetics

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    Rajagopalan, G., Smart, M. K., Cheng, S., Krco, C. J., Johnson, K. L., & David, C. S. (2003). Expression and function of HLA-DR3 and DQ8 in transgenic mice lacking functional H2-M. Tissue Antigens, 62(2), 149-161. https://doi.org/10.1034/j.1399-0039.2003.00088.x