title: Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo.
abstract: CD8(+) T cells (T(CD8+)) differentiate into effector cells following recognition of specific peptide-major histocompatibility complex (MHC) class I complexes (pMHC-I) on the surface of professional APCs (pAPCs), such as dendritic cells. Antigenic pMHC-I can be generated from two spatially distinct sources. The direct presentation pathway involves generation of peptide from protein substrate synthesized within the cell that is presenting the pMHC-I. Alternatively, the cross presentation pathway involves presentation of antigen that is not synthesized within the presenting cell, but is derived from exogenous proteins synthesized within other donor cells. The mechanisms by which cross presentation of exogenous antigens occur in vivo remain controversial. The C-type lectin scavenger receptor A (SR-A) has been implicated in a number of potential cross presentation pathways, including the presentation of peptide bound to heat shock proteins, such as glycoprotein 96 (gp96), and the transfer of pMHC-I from a donor cell to the pAPC. We demonstrate here that initiation of T(CD8+) responses is normal in mice lacking SR-A, and that the redundancy of ligand binding exhibited by the SR family is likely to be an important mechanism that ensures cross presentation in vivo. These observations emphasize the requirement to target multiple receptors and antigen-processing pathways during the rational design of vaccines aimed at eliciting protective T(CD8+).
authors.affiliation: Department of Microbiology and Immunology, Milton S. Hershey College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
authors.forename: Eric F
authors.initials: EF
authors.lastname: Tewalt
authors.forename: Jason C
authors.initials: JC
authors.lastname: Maynard
authors.forename: Julie Jo
authors.initials: JJ
authors.lastname: Walters
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Schell
authors.forename: Brent L
authors.initials: BL
authors.lastname: Berwin
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Nicchitta
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Norbury
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D037282:Calreticulin / Q000276:immunology; D002460:Cell Line; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D018274:Electroporation; D005260:Female; D015395:Histocompatibility Antigens Class I; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D010047:Ovalbumin; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D037282:Calreticulin; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D051117:Scavenger Receptors, Class A; C053387:endoplasmin; D007371:Interferon-gamma; D010047:Ovalbumin