Autor: |
Hederer, Rosemarie A., Chandler, Phillip R., Dyson, P. Julian, Antoniou, Antony N., Millrain, Margaret M., Mellor1, Andrew L., Simpson, Elizabeth, Robinson, Peter J. |
Zdroj: |
Transplantation; January 1996, Vol. 61 Issue: 2 p299-304, 6p |
Abstrakt: |
Single amino acid disparities in MHC class I molecules can elicit transplantation responses. Since β2 microglobulin (β2m) is noncovalently associated with class I antigens on the cell membrane we investigated whether the single amino acid polymorphism at position 85 (Asp→ Ala) in the mouse β2m molecule can cause skin graft rejection. A B2mbtransgene was introduced into CBA(B2ma) mice which subsequently expressed both forms of β2m. Skin from these CBA β2mbtransgenic mice was not rejected by the parental CBA strain. Previous studies showed that cytotoxic T lymphocyte (CTL) responses directed against β2mbuse H2Kbas a restriction element. We therefore produced mice expressing H2Kband H2Abas well as β2mbby crossing CBA.β2mbmice with either CBA.Kb(CBK) transgenic mice or C3H.SW mice and used these as skin graft donors for β2mbnegative littermates. In both cases rejection of transgenic skin only occurred when mice had received both aβ2mbgraft and an H2-disparate allograft lying adjacent in the same site. Introduction of the male specific antigen, H-Y, as a helper determinant did not result in rejection of β2mbskin. Neither did two CTL determinants (P91A and β2mb) on the same graft complement one another to elicit a transplantation response. Prior immunisation with tissues expressing the β2m disparity alone did not generate in vivoor in vitroβ2mb-specific CTL responses, suggesting that this single amino acid difference is not sufficient to elicit a CTL or helper T cell response. |
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