Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts.

The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When B10.AQR grafts were transplanted onto B10.T(6R) recipients, a significant prolongation of the survival time was observed, while 50% of the UVB-treated grafts were not rejected at all. However, in the opposite direction--i.e., B10.T(6R) grafts onto B10.AQR recipients, no significant prolongation of the survival was observed. To test whether this effect was due to a difference in susceptibility of the donor skin to UVB irradiation or to a different immune response in the recipients, (B10.T(6R) x B10.AQR) grafts were transplanted onto the parent strains. Similar results were obtained, in that UVB-treated grafts did not show a prolonged survival in B10.AQR recipients, whereas a significant prolongation (50% of the grafts survived more than 100 days) was observed in B10.T(6R) recipients. UVB-treated (B10.T(6R) x B10.AQR)F1 grafts were also transplanted onto (B10.T(6R) x C57B1/10)F1, (B10.AQR x C57B1/10)F1, (B10.T(6R) x Balb/c)F1 and (B10.AQR x Balb/c)F1 recipients--but in none of these combinations was a prolonged survival time observed. These data suggest that, in contrast to all in vitro experiments, the abrogation of the immune response by UVB treatment of the stimulator cells is, in vivo, not a general phenomenon. The genetic constitution of the responder mice seems to play an important role in determining whether or not an immune response takes place.

Decreased expression of HLA class II antigens on human uveal melanoma cells after in vivo X-ray irradiation.

In order to determine the presence of HLA antigens on human uveal melanomas, we tested anti-HLA monoclonal antibodies on tissue sections of these tumors. A great variety in expression of HLA class I and II antigens was present. A significantly lower expression of HLA class II antigens was present on uveal melanomas that had been irradiated before enucleation. These tumors lacked a lymphocytic infiltrate in comparison with nonirradiated tumors. These data suggest that radiotherapy affects expression of histocompatibility antigens on tumors.

UV sensitivity of human keratinocyte and Langerhans cell-expressed HLA-DR antigens: a comparison.

HLA-DR expression on human keratinocytes (KC) was induced in vivo by intradermal injection of purified protein derivative of tuberculin (PPD). Neither preceding nor subsequent exposure of the PPD injection site to a dose of approximately 2 MED of UVB radiation abolished KC HLA-DR, though subsequent irradiation caused a slight diminution in the intensity of the antigen expression. By contrast, epidermal Langerhans cell (LC) HLA-DR and T6 expressions in normal epidermis were greatly reduced by an identical dose of UVB. Pemphigus antigen on the surface of KC was not affected by irradiation or PPD injection.

Effect of UVB radiation on the biosynthesis of HLA-DR antigens.

HLA-DR molecules on the surface of immunocompetent cells are thought to represent target structures for the immunomodulating effects of UV radiation during the induction of an immune response. We therefore investigated the effect of UVB radiation on the de novo synthesis of HLA-DR-gamma-chains in the cytoplasm and the expression of alpha- and beta-chains on the surface of the human lymphoblastoid B-cell line Raji. Raji cells were UVB irradiated before biochemical experiments were performed. Cells were then metabolically labeled or radioiodinated and detergent lysates immunoprecipitated using antibodies directed against the gamma- or the alpha- and beta-chain of the HLA-DR molecule. Over a wide dose range, UVB-irradiated Raji cells were shown to still express HLA-DR determinants on their surface and, even more importantly, to be capable of synthesizing HLA-DR-alpha, beta- and gamma-chains in a normal fashion. Despite this, the functional capacity of Raji cells was impaired in a dose-dependent manner. UV radiation thus seems to exert its immunomodulating effects primarily at a different level than the incriminated immune-response-associated antigens, which are expressed as recognition structures on the surface of immunocompetent cells.