PD-1 and CD73 on naive CD4 T cells synergistically limit responses to self.

Vaccination with self- and foreign peptides induces weak and strong expansion of antigen-specific CD4 T cells, respectively, but the mechanism is not known. In the present study, we used computational analysis of the entire mouse major histocompatibility complex class II peptidome to test how much of the naive CD4 T cell repertoire specific for self-antigens was shaped by negative selection in the thymus and found that negative selection only partially explained the difference between responses to self and foreign. In naive uninfected and unimmunized mice, we identified higher expression of programmed cell death protein 1 (PD-1) and CD73 mRNA and protein on self-specific CD4 T cells compared with foreign-specific CD4 T cells.

Olfr2-positive macrophages originate from monocytes proliferate in situ and present a pro-inflammatory foamy-like phenotype.

Aims: Olfactory receptor 2 (Olfr2) has been identified in a minimum of 30% of vascular macrophages, and its depletion was shown to reduce atherosclerosis progression. Mononuclear phagocytes, including monocytes and macrophages within the vessel wall, are major players in atherosclerosis. Single-cell RNA sequencing studies revealed that atherosclerotic artery walls encompass several monocytes and vascular macrophages, defining at least nine distinct subsets potentially serving diverse functions in disease progression.

Immunodominant MHC-II (Major Histocompatibility Complex II) Restricted Epitopes in Human Apolipoprotein B.

Background: CD (cluster of differentiation) 4 T-cell responses to APOB (apolipoprotein B) are well characterized in atherosclerotic mice and detectable in humans. CD4 T cells recognize antigenic peptides displayed on highly polymorphic HLA (human leukocyte antigen)-II. Immunogenicity of individual APOB peptides is largely unknown in humans.

A humanized β integrin knockin mouse reveals localized intra- and extravascular neutrophil integrin activation in vivo.

β integrins are leukocyte-specific adhesion molecules that are essential for leukocyte recruitment. The lack of tools for reporting β integrin activation in mice hindered the study of β integrin-related immune responses in vivo. Here, we generated a humanized β integrin knockin mouse strain by targeting the human β integrin coding sequence into the mouse Itgb2 locus to enable imaging of β integrin activation using the KIM127 (extension) and mAb24 (high-affinity) reporter antibodies.