In Vitro and in Vivo Evidence for High Frequency of I-Ab-Reactive CD4+ T Cells in HLA-DQ or HLA-DRA Transgenic Mice Lacking Endogenous MHC Class I and/or Class II Expression

Tatsuro Ishimoto, Ken Yamamoto, Yoshinori Fukui, Yasuhiko Fukuda, Kiyohiko Dohi, Takehiko Sasazuki

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3 Citations (Scopus)

Abstract

Although T cells are educated to recognize foreign antigenic peptides in the context of self MHC molecules during their development in the thymus, peripheral T cells also recognize allo- and xeno-MHC molecules. The lower frequency of xeno-MHC-reactive T cells than that of allo-MHC-reactive T cells is often explained by the difference in the degree of homology between xeno- or allo-MHC and self MHC molecules, as well as by the species barrier of the molecules involved in immune recognition. To distinguish these two possibilities, we estimated the frequency of I-Ab-reactive CD4+ T cells selected by HLA-DQ or DRαEβb molecules, using HLA-DQ6 and HLA-DRA transgenic C57BL/6 (B6) mice lacking endogenous MHC class I and/or class II molecules (DQ6A% and DRα30A%β2%). CD4+ lymph node T cells from DQ6A% and DRα30A%β2% showed the strong proliferative response to I-Ab molecules. In addition, DQ6A% and DRα30A%β2% rejected the skin graft from mice expressing I-Ab molecules irrespective of MHC class I expression, indicating that the CD4+ T cells recognizing I-Ab molecules are directly involved in this rejection. The estimated frequency of I-Ab-reactive CD4+CD8- thymocytes in DRα30A%β2% and DQ6A% was comparable with that observed in the MHC class II-disparate strains. Our findings thus indicate that CD4+ T cells selected to mature on xeno-MHC class II molecules such as HLA-DQ6 or DRαEβb, when these molecules are expressed in mice, recognize I-Ab molecules as allo-MHC class II, despite the less structural homology.

Original languageEnglish
Pages (from-to)3717-3722
Number of pages6
JournalJournal of Immunology
Volume159
Issue number8
Publication statusPublished - Oct 15 1997

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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