Ra. Hederer et al., ACCEPTANCE OF SKIN-GRAFTS BETWEEN MICE BEARING DIFFERENT ALLELIC FORMS OF BETA(2)-MICROGLOBULIN, Transplantation, 61(2), 1996, pp. 299-304
Single amino acid disparities in MHC class I molecules can elicit tran
splantation responses. Since beta 2 microglobulin (beta(2)m) is noncov
alently associated with class I antigens on the cell membrane we inves
tigated whether the single amino acid polymorphism at position 85 (Asp
--> Ala) in the mouse beta(2)m molecule can cause skin graft rejectio
n. A B2m(b) transgene was introduced into CBA(B2m(a)) mice which subse
quently expressed both forms of beta(2)m. Skin from these CBA beta(2)m
(b) transgenic mice was not rejected by the parental CBA strain. Previ
ous studies showed that cytotoxic T lymphocyte (CTL) responses directe
d against beta(2)m(b) use H2K(b) as a restriction element. We therefor
e produced mice expressing H2K(b) and H2A(b) as well as beta 2m(b) by
crossing CBA.beta(2)m(b) mice with either CBA.K-b (CBK) transgenic mic
e or C3H.SW mice and used these as skin graft donors for beta(2)m(b) n
egative littermates. In both cases rejection of transgenic skin only o
ccurred when mice had received both a beta(2)m(b) graft and an H2-disp
arate allograft lying adjacent in the same site. Introduction of the m
ale specific antigen, H-Y, as a helper determinant did not result in r
ejection of beta(2)m(b) skin. Neither did two CTL determinants (P91A a
nd beta(2)m(b)) on the same graft complement one another to elicit a t
ransplantation response. Prior immunisation with tissues expressing th
e beta(2)m disparity alone did not generate in vivo or in vitro beta(2
)m(b)-specific CTL responses, suggesting that this single amino acid d
ifference is not sufficient to elicit a CTL or helper T cell response.