A critical, invariant chain-independent role for H2-M in antigen presentation.
Antigen presentation by MHC class II (class II) is facilitated by the accessory molecules, invariant chain (Ii) and H2-M. Ii associates with class II during biosynthesis and promotes transport of class II to Ag-loading compartments. One function of H2-M is the removal of Ii fragments from MHC class II. We have previously demonstrated that Ii-deficient mice, unlike class II-deficient mice, are resistant to L. major infection. In the present study, we found that H2-M-deficient (H2-M0) mice were susceptible to progressive infection with L. major. The dispensability of Ii for control of L. major allowed genetic analysis of whether H2-M functions by association with or independently of Ii. In contrast to Ii-deficient (Ii0) mice, Ii0H2-M0 mice were as susceptible to L. major as H2-M0 mice. Thus, H2-M has an essential, Ii-independent function during presentation of microbial pathogens.
Swier
K
K
Department of Medicine, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Illinois 60637, USA.
Brown
D R
DR
Bird
J J
JJ
Martin
W D
WD
Van Kaer
L
L
Reiner
S L
SL
D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000502:physiology*; D004198:Disease Susceptibility; D006681:HLA-D Antigens / Q000235:genetics / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology*; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D000944:Antigens, Differentiation, B-Lymphocyte; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain