The macrophage scavenger receptor type A directs modified proteins to antigen presentation

Scavenger receptors constitute a family of cell surface receptors that internalize endotoxins, oxidized low-density lipoproteins (oxLDL) and other proteins with clustered negative charges for degradation in macrophages. They were recently proposed to play a role in antigen presentation but the type of scavenger receptor involved in this process has not been known. In this report, we have examined the cellular immune responses to modified proteins in mice lacking the SR-A scavenger receptor (SRAKO) and their wild-type (ICR) controls. While spleen cells of ICR mice immunized with maleylated murine serum albumin (Mal-MSA) exhibit strong proliferative responses to the antigen, no such responses were found in SRAKO mice. However, addition of SR-A+ antigen-presenting cells from ICR mice unmasked proliferative responses to Mal-MSA in spleen cultures of immunized SRAKO mice. Similarly, addition of SR-A+ antigen-presenting cells was necessary to detect T cell responses in spleen cultures of oxLDL-immunized SRAKO mice. This indicates that SR-A can mediate uptake of modified antigens for presentation to antigen-specific T cells. The fact that cellular immunity developed in SRAKO mice implies that other scavenger receptor(s) also internalize modified antigens for presentation in vivo. These observations show that scavenger receptors participate in immune recognition of oxidized protein antigens; this system may be important for recognition of damaged macromolecules but could also play a role in autoimmunity.