| First Author | Oukka M | Year | 1997 |
| Journal | Eur J Immunol | Volume | 27 |
| Issue | 12 | Pages | 3499-506 |
| PubMed ID | 9464840 | Mgi Jnum | J:45133 |
| Mgi Id | MGI:1194439 | Doi | 10.1002/eji.1830271251 |
| Citation | Oukka M, et al. (1997) Major histocompatibility complex class I presentation of exogenously acquired minor alloantigens initiates skin allograft rejection. Eur J Immunol 27(12):3499-506 |
| abstractText | Major histocompatibility complex (MHC) class I molecules present peptides from endogenous proteins. However, in some cases class I-restricted peptides can also derive from exogenous antigens. This MHC class I exogenous presentation could be involved in minor histocompatibility antigen (mHAg)-disparate allograft rejection when donor alloantigens are not expressed in graft antigen-presenting cells (APC) that initiate the rejection mechanism. Here we addressed this question by using a skin graft experimental model where donors (H-2b or H-2d Tg beta-gal mice) expressed the mHAg like beta-galactosidase (beta-gal) in keratinocytes but not in Langerhans' cells (LC) which have an APC function. Rejection of Tg beta-gal skin by a beta-gal-specific CD8 cytotoxic T lymphocyte (CTL) effector mechanism should require presentation by donor and/or recipient LC of MHC class I-restricted peptides of exogenous beta-gal shed by keratinocytes. Indeed, our results showed that 1) H-2b Tg beta-gal skin was rejected by H-2bxs and H-2bxd recipients; 2) rejection was mediated by beta-gal-specific CD8+ CTL effectors; and 3) H-2bxd mice having rejected H-2b Tg beta-gal skin generated beta-gal-specific CTL restricted by H-2b and H-2d class I molecules and rejected subsequently grafted H-2d Tg beta-gal skin in an accelerated fashion, demonstrating that recipient LC have presented exogenous beta-gal-derived MHC class I epitopes. These results lead to the conclusion that MHC class I exogenous presentation of donor mHAg can initiate allograft rejection. |
