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

Scavenger receptors constitute a family of cell surface receptors that inte rnalize endotoxins, oxidized low-density lipoproteins (oxLDL) and other pro teins 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 (I CR) controls. White spleen cells of ICR mice immunized with maleylated muri ne serum albumin (Mal-MSA) exhibit strong proliferative responses to the an tigen, no such responses were found in SRAKO mice. However, addition of SR- A(+) antigen-presenting cells from ICR mice unmasked proliferative response s to Mal-MSA in spleen cultures of immunized SRAKO mice. Similarly, additio n of SR-A(+) antigen-presenting cells was necessary to detect T cell respon ses in spleen cultures of oxLDL-immunized SRAKO mice. This indicates that S R-A can mediate uptake of modified antigens for presentation to antigen-spe cific T cells. The fact that cellular immunity developed in SRAKO mice impl ies that other scavenger receptor(s) also internalize modified antigens for presentation in vivo. These observations show that scavenger receptors par ticipate in immune recognition of oxidized protein antigens; this system ma y be important for recognition of damaged macromolecules but could also pla y a role in autoimmunity.