Immune Surveillance by Natural IgM Is Required for Early Neoantigen Recognition and Initiation of Adaptive Immunity

被引:26
作者
Atif, Shaikh M. [1 ]
Gibbings, Sophie L. [1 ]
Redente, Elizabeth F. [1 ]
Camp, Faye A. [2 ]
Torres, Raul M. [2 ]
Kedl, Ross M. [2 ]
Henson, Peter M. [1 ,2 ]
Jakubzick, Claudia, V [1 ,2 ]
机构
[1] Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA
[2] Univ Colorado, Dept Immunol & Microbiol, Aurora, CO USA
基金
美国国家卫生研究院;
关键词
Ly6C(+) monocytes; XCR1(+) Batf3(+) dendritic cells; neoantigens; cancer; natural; DENDRITIC CELLS; H-Y; T-CELLS; HISTOCOMPATIBILITY ANTIGEN; INFLUENZA-VIRUS; CD8(+); ANTIBODY; LUNG; AUTOANTIBODIES; EXPRESSION;
D O I
10.1165/rcmb.2018-0159OC
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Early recognition of neoantigen-expressing cells is complex, involving multiple immune cell types. In this study, in vivo, we examined how antigen-presenting cell subtypes coordinate and induce an immunological response against neoantigen-expressing cells, particularly in the absence of a pathogen-associated molecular pattern, which is normally required to license antigen-presenting cells to present foreign or self-antigens as immunogens. Using two reductionist models of neoantigen-expressing cells and two cancer models, we demonstrated that natural IgM is essential for the recognition and initiation of adaptive immunity against neoantigen-expressing cells. Natural IgM antibodies form a cellular immune complex with the neoantigen-expressing cells. This immune complex licenses surveying monocytes to present neoantigens as immunogens to CD4(+) T cells. CD4(+) T helper cells, in turn, use CD40L to license cross-presenting CD40(+) Batf3(+) dendritic cells to elicit a cytotoxic T cell response against neoantigen-expressing cells. Any break along this immunological chain reaction results in the escape of neoantigen-expressing cells. This study demonstrates the surprising, essential role of natural IgM as the initiator of a sequential signaling cascade involving multiple immune cell subtypes. This sequence is required to coordinate an adaptive immune response against neoantigen-expressing cells.
引用
收藏
页码:580 / 591
页数:12
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