TY - JOUR
T1 - Allorecognition in a Basal Chordate Consists of Independent Activating and Inhibitory Pathways
AU - McKitrick, Tanya R.
AU - Muscat, Christina C.
AU - Pierce, James D.
AU - Bhattacharya, Deepta
AU - De Tomaso, Anthony W.
N1 - Funding Information:
We thank K. Palmeri, K. Ishizuka, and M. Caun for help with animal rearing; L. Jerabek, M. Inlay, T. Serwold, and I. Weissman for help with antibody production; and J. Carlyle and N. Netuschil for critical reading of the manuscript and helpful discussions. This research was supported by NIH grants AI041588 and DK045762 to A.W.D. and EPA STAR fellowship 91631401-0 and NIH grant 1F31A1075606-01A2 to T.R.M.
PY - 2011/4/22
Y1 - 2011/4/22
N2 - Histocompatibility in the basal chordate Botryllus schlosseri is controlled by the polymorphisms of a single gene: the fuhc. A polymorphic candidate receptor (fester) appeared to play roles in both initiating the reaction and discriminating between fuhc alleles. Here we report the characterization of a related protein, uncle fester. uncle fester is not polymorphic, and although coexpressed with fester, has different functional properties. Loss-of-function studies demonstrate that uncle fester was required for incompatible reactions but has no role in interactions between compatible individuals. Furthermore, stimulation with monoclonal antibodies could initiate a rejection phenotype on a single colony, and in both assays the severity of the rejection could be manipulated. These findings suggest that allorecognition in Botryllus consists of independent pathways that control compatible and incompatible outcomes that are integrated within the interacting cells, and may provide insight into basal processes conserved in allorecognition responses throughout the metazoa.
AB - Histocompatibility in the basal chordate Botryllus schlosseri is controlled by the polymorphisms of a single gene: the fuhc. A polymorphic candidate receptor (fester) appeared to play roles in both initiating the reaction and discriminating between fuhc alleles. Here we report the characterization of a related protein, uncle fester. uncle fester is not polymorphic, and although coexpressed with fester, has different functional properties. Loss-of-function studies demonstrate that uncle fester was required for incompatible reactions but has no role in interactions between compatible individuals. Furthermore, stimulation with monoclonal antibodies could initiate a rejection phenotype on a single colony, and in both assays the severity of the rejection could be manipulated. These findings suggest that allorecognition in Botryllus consists of independent pathways that control compatible and incompatible outcomes that are integrated within the interacting cells, and may provide insight into basal processes conserved in allorecognition responses throughout the metazoa.
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U2 - 10.1016/j.immuni.2011.01.019
DO - 10.1016/j.immuni.2011.01.019
M3 - Article
C2 - 21497115
AN - SCOPUS:79954961338
SN - 1074-7613
VL - 34
SP - 616
EP - 626
JO - Immunity
JF - Immunity
IS - 4
ER -