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The Journal of Immunology, Vol 159, Issue 8 3717-3722, Copyright © 1997 by American Association of Immunologists

ARTICLES

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

T Ishimoto, K Yamamoto, Y Fukui, Y Fukuda, K Dohi and T Sasazuki
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka.

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 DR alpha E beta b molecules, using HLA-DQ6 and HLA-DRA transgenic C57BL/6 (B6) mice lacking endogenous MHC class I and/or class II molecules (DQ6A0/0 and DR alpha 30A0/0 beta 20/0). CD4+ lymph node T cells from DQ6A0/0 and DR alpha 30A0/0 beta 20/0 showed the strong proliferative response to I-Ab molecules. In addition, DQ6A0/0 and DR alpha 30A0/0 beta 20/0 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 DR alpha 30A0/0 beta 20/0 and DQ6A0/0 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 DR alpha E beta b, when these molecules are expressed in mice, recognize I-Ab molecules as allo-MHC class II, despite the less structural homology.


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 Proc. Natl. Acad. Sci. USAHome page
L. Madsen, N. Labrecque, J. Engberg, A. Dierich, A. Svejgaard, C. Benoist, D. Mathis, and L. Fugger
Mice lacking all conventional MHC class II genes
PNAS, August 31, 1999; 96(18): 10338 - 10343.
[Abstract] [Full Text] [PDF]


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