Autologous Mixed Lymphocyte Reaction Induced in Mice by Xenogeneic Immunization with Soluble HLA-DR Antigens

Abstract

In order to study the effects of in vivo immunization of mice with xenogeneic human MHC class II antigens, mice were injected with cellular or purified HLA-DR antigens and their T cell proliferative response tested in secondary in vitro cultures. Our data indicated that small amounts of soluble HLA-DR antigens were able to prime the animals and that the xenogeneic MLR depends on the expression of HLA class II antigens on the stimulating cells. No proliferative response was obtained with cells expressing only HLA class I molecules. Using a pannel of human cells with various haplotypes our results showed that non polymorphic determinants of HLA class II antigens trigger dominantly the murine T cells and that the xenogeneic response was inhibited by anti I-E but not anti I-A or anti-HLA class II MAb. In addition, our data demonstrated that such immunization proceedure could also stimulate a murine auto-MLR since HLA class II primed murine lymph node cells reacted against autologous spleen cells or dendritic cells. These results suggested that HLA class II antigens acting as nominal antigens can induce murine T cells to recognize cross-reactive determinants at the surface of autologous cells.