Absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope.
Tapasin edits the peptide repertoire presented to CD8(+) T cells by favoring loading of slow off-rate peptides on MHC I molecules. To investigate the role of tapasin on T cell immunodominance we used poxvirus viral vectors expressing a polytope of lymphocytic choriomeningitis virus epitopes with different off-rates. In tapasin-deficient mice, responses to subdominant fast off-rate peptides were clearly favored. This alteration of the CD8(+) T cell hierarchy was a consequence of tapasin editing and not a consequence of the alteration of the T cell repertoire in tapasin-deficient mice, because bone marrow chimeric mice (wild-type recipients reconstituted with tapasin knockout bone marrow) showed the same hierarchy as the tapasin knockout mice. Tapasin editing is therefore a contributing factor to the phenomenon of immunodominance. Although tapasin knockout cells have low MHC I surface expression, Ag presentation was efficient and resulted in strong T cell responses involving T cells with increased functional avidity. Therefore, in this model, tapasin-deficient mice do not have a reduced but rather have an altered immune response.
Boulanger
Denise S M
DS
Cancer Research UK Centre, Cancer Sciences Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
Oliveira
Roberta
R
Ayers
Lisa
L
Prior
Stephen H
SH
James
Edward
E
Williams
Anthony P
AP
Elliott
Tim
T
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D026901:Membrane Transport Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D026901:Membrane Transport Proteins; C107762:tapasin