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Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo
Author(s) -
Tewalt Eric F.,
Maynard Jason C.,
Walters Julie Jo,
Schell Amanda M.,
Berwin Brent L.,
Nicchitta Christopher V.,
Norbury Christopher C.
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02861.x
Subject(s) - cross presentation , scavenger receptor , microbiology and biotechnology , antigen presentation , major histocompatibility complex , cytotoxic t cell , biology , cd8 , antigen , receptor , priming (agriculture) , antigen presenting cell , antigen processing , effector , mhc class i , in vivo , t cell , immunology , immune system , in vitro , biochemistry , genetics , lipoprotein , botany , germination , cholesterol
Summary 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+ .