MHC class Ib-restricted cells contribute to antilisterial immunity: evidence for Qa-1b as a key restricting element for Listeria-specific CTLs.
Subclinical infection of BALB/c mice with the intracellular pathogen Listeria monocytogenes results in the development of MHC class Ia- and Ib-restricted CTLs. L. monocytogenes-infected TAP-/- bone marrow macrophage targets are not lysed by MHC class Ia- or Ib-restricted CTLs, showing a requirement for transport of peptides into the endoplasmic reticulum for development of the MHC class Ib-peptide target. L. monocytogenes-infected B6.Tla(a)-derived bone marrow macrophages (Kb Qa-1a) are not lysed by BALB/c (Kd Qa-1b)-derived antilisterial CTLs, confirming an earlier finding that the Ib-restricting element is T region encoded. We have further determined that Qa-1b is a restricting element for antilisterial CTLs using L. monocytogenes-infected Qa-1b-transformed mouse L cells as well as human-derived HeLa cells as target populations. These L. monocytogenes-infected Qa-1b-transformed cell lines are lysed by BALB/c (Qa-1b)- or C57BL/6 (Qa-1b)-derived antilisterial CTLs, but are not lysed by B6.AKM (Qa-1a)-derived antilisterial CTLs. Using L. monocytogenes-infected targets, we found that MHC class Ia- and Ib-restricted CTLs are evident within 4 days following infection, peak on day 5 following infection, and although Ib-restricted CTLs disappear by day 6 postinfection, la-restricted antilisterial CTL activity can still be detected. These results demonstrate that Qa-1b is a restricting element for antilisterial CTLs, and expression of the MHC class Ib-presented target at the cell surface is TAP dependent. In addition, these results show that following L. monocytogenes infection, MHC class Ib-restricted CTLs are evident in vivo.
Bouwer
H G
HG
Immunology Research, Veterans Affairs Medical Center and Earle A. Chiles Research Institute, Portland, Oregon 97201, USA.
Seaman
M S
MS
Forman
J
J
Hinrichs
D J
DJ
D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens