title: An MHC class Ib-restricted CD8+ T cell response to lymphocytic choriomeningitis virus.
abstract: Conventional MHC class Ia-restricted CD8(+) T cells play a dominant role in the host response to virus infections, but recent studies indicate that T cells with specificity for nonclassical MHC class Ib molecules may also participate in host defense. To investigate the potential role of class Ib molecules in anti-viral immune responses, K(b-/-)D(b-/-)CIITA(-/-) mice lacking expression of MHC class Ia and class II molecules were infected with lymphocytic choriomeningitis virus (LCMV). These animals have a large class Ib-selected CD8(+) T cell population and they were observed to mediate partial (but incomplete) virus clearance during acute LCMV infection as compared with K(b-/-)D(b-/-)β(2)-microglobulin(-/-) mice that lack expression of both MHC class Ia and class Ib molecules. Infection was associated with expansion of splenic CD8(+) T cells and induction of granzyme B and IFN-γ effector molecules in CD8(+) T cells. Partial virus clearance was dependent on CD8(+) cells. In vitro T cell restimulation assays demonstrated induction of a population of β(2)-microglobulin-dependent, MHC class Ib-restricted CD8(+) T cells with specificity for viral Ags and yet to be defined nonclassical MHC molecules. MHC class Ib-restricted CD8(+) T cell responses were also observed after infection of K(b-/-)D(b-/-)mice despite the low number of CD8(+) T cells in these animals. Long-term infection studies demonstrated chronic infection and gradual depletion of CD8(+) T cells in K(b-/-)D(b-/-)CIITA(-/-) mice, demonstrating that class Ia molecules are required for viral clearance. These findings demonstrate that class Ib-restricted CD8(+) T cells have the potential to participate in the host immune response to LCMV.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: David C
authors.initials: DC
authors.lastname: Jay
authors.forename: Jared D
authors.initials: JD
authors.lastname: Fairbanks
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.forename: Peter E
authors.initials: PE
authors.lastname: Jensen
mesh_terms: D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D006224:Cricetinae; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014709:Vero Cells; D019562:Viral Load / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators
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