Major histocompatibility complex-restricted and unrestricted activation of helper T cell lines by liposome-bound antigens

Helper T lymphocytes recognize foreign antigen together with class II major histocompatibility complex (Mhc) molecules on the surface of antigen-presenting cells (APC). However, it is not known in what form soluble protein antigens are presented to T cells. The difficulty of serologically demonstrating the presence of soluble antigen on the surface of APC, the observed rapid degradation of antigen by these cells, and the finding that under special circumstances peptides of a certain protein are more antigenic that the whole molecule have led to the notion that foreign antigens must be rendered immunogenic for helper T cells by internalization, processing (probably involving enzymatic fragmentation), and redisplay on the membrane of APC in association with class II Mhc molecules. To analyze antigen recognition by helper T cells and to assess the biological significance of antigen processing, we have constructed liposomes that carry inserted class II Mhc molecules and a protein antigen coupled covalently to one of the lipid constituents of the artificial membrane. We demonstrate here that such liposomes are capable of inducing proliferative responses of long-term cultured T-cell clones, and interleukin-2 (Il-2) production by a T-cell hybridoma in an antigen-specific, Mhc-restricted fashion, in the absence of antigen-presenting cells. The responses require the presence of foreign antigen class II molecules on the same lipid vesicles. The magnitude of responses is critically dependent on the lipid composition, the density of bound antigen, and the concentration of liposomes in cell cultures. In case of at least T-cell lines, the requirement for Mhc-restriction can be overcome that is, liposomes carrying foreign antigen along (but not the antigen itself in soluble form) induce responses provided that the density of antigen on vesicles is high enough. That the liposomes described here represent a truly cell-free system of T-cell activation is further supported by the finding that T cells fail to present liposome-bound antigen to each other.