Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo

Eric F. Tewalt, Jason C. Maynard, Julie Jo Walters, Amanda M. Schell, Brent L. Berwin, Christopher V. Nicchitta, Christopher C. Norbury

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

CD8+ T cells (TCD8+) 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 TCD8+ 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 TCD8+.

Original languageEnglish (US)
Pages (from-to)480-491
Number of pages12
JournalImmunology
Volume125
Issue number4
DOIs
StatePublished - Dec 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Tewalt, E. F., Maynard, J. C., Walters, J. J., Schell, A. M., Berwin, B. L., Nicchitta, C. V., & Norbury, C. C. (2008). Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo. Immunology, 125(4), 480-491. https://doi.org/10.1111/j.1365-2567.2008.02861.x