Impaired response to Listeria in H2-M3-deficient mice reveals a nonredundant role of MHC class Ib-specific T cells in host defense.
The major histocompatibility complex (MHC) class Ib molecule H2-M3 primes the rapid expansion of CD8+ T cells by presenting N-formylated bacterial peptides. However, the significance of H2-M3-restricted T cells in host defense against bacteria is unclear. We generated H2-M3-deficient mice to investigate the role of H2-M3 in immunity against Listeria monocytogenes (LM), a model intracellular bacterial pathogen. H2-M3-deficient mice are impaired in early bacterial clearance during primary infection, with diminished LM-specific CD8+ T cell responses and compromised innate immune functions. Although H2-M3-restricted CD8+ T cells constitute a significant proportion of the anti-listerial CD8+ T cell repertoire, the kinetics and magnitude of MHC class Ia-restricted T cell responses are not altered in H2-M3-deficient mice. The fact that MHC class Ia-restricted responses cannot compensate for the H2-M3-mediated immunity suggests a nonredundant role of H2-M3 in the protective immunity against LM. Thus, the early H2-M3-restricted response temporally bridges the gap between innate and adaptive immune responses, subsequently affecting the function of both branches of the immune system.
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Honglin
H
Xu
Taehoon
T
Chun
Hak-Jong
HJ
Choi
Bin
B
Wang
Chyung-Ru
CR
Wang
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008087:Listeria / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D018984:Epitopes, T-Lymphocyte; C078177:H2-M3 antigen; D015395:Histocompatibility Antigens Class I