This invention relates, at least in part, to compositions comprising synthetic nanocarriers and immunosuppressants that result in immune suppressive effects. Such compositions can further comprise antigen and provide antigen-specific tolerogenic immune responses.

The present invention relates an in vitro method for detecting class II restricted CD4+ T cells in a sample. Herein a sample is contacted with an isolated complex of an MHC class II molecule and a peptide. This peptide comprises an MHC class II restricted T cell epitope of an antigenic protein and immediately adjacent thereof, or separated by a linker of at most 7 amino acids a sequence with a [CST]-xx-C or C-xx-[CST] motif. CD4+ T cells are detected by measuring the binding of the complex with cells in the sample, wherein the binding of the complex to a cell is indicative for the presence of CD4+ T cells in the sample. The present invention further relates to an isolated complex of an MHC Class II molecule and a peptide comprising an MHC class II restricted T cell epitope of an antigenic protein and immediately adjacent thereof, or separated by a linker of at most 7 amino acids a sequence with a [CST]-xx-C or C-xx-[CST] motif.

Multiparametric analysis is performed at the single cell level of biological samples obtained from an individual during pregnancy to obtain a determination of changes in immune cell subsets, which changes include, without limitation, altered activation states of proteins involved in signaling pathways. Changes occur in signaling pathways of these immune cells that are predictive of propensity to develop preeclampsia in the pregnancy.

The disclosure provides methods of determining patient populations amenable or suitable for immunomodulatory treatment of disease such as cancer by measuring the relative or absolute levels of T-cell sub-populations correlated with disease such as cancer.

Disclosed are synthetic nanocarrier compositions, and related methods, comprising therapeutic protein APC presentable antigens and immunosuppressants that provide tolerogenic immune responses specific to therapeutic proteins.

Disclosed are synthetic nanocarrier compositions, and related methods, comprising immunosuppressants and MHC Class II-restricted epitopes of an allergen that provide tolerogenic immune responses specific to the allergen.

Provided are methods involving the assaying of a labeled cell suspension, e.g., to detect cancer-related cells, populations ON thereof and/or screen for metastatic cancer. Labeled cell suspensions may be assayed to detect whether a tumor infiltrating lymphocyte (TIL) population is present in a cellular suspension of a subject. Cancer-related cell populations of interest include, e.g., those expressing one or more markers, including where the markers are members of a marker panel. Markers assayed may vary depending on the context and may include protein markers, nucleic acid markers, cell cycle markers, DNA content markers, and the like. Useful markers include one or more immune checkpoint markers and/or one or more immune cell-type markers, including where the marker(s) assayed are part of one or more panels of markers. Also provided are methods of treating a subject for a neoplasia based on the outcome of an assay of a labeled cell suspension of sample from a subject. Kits for practicing the described methods are also provided.

The present invention relates to methods for labeling intracellular and extracellular targets of leukocytes, as well as to kits for performing said methods.

Disclosed are synthetic nanocarrier compositions, and related methods, comprising immunosuppressants and MHC Class II-restricted epitopes of an allergen that provide tolerogenic immune responses specific to the allergen.

The invention provides methods of isolating CD 127.sup.lo/− immunosuppressive regulatory T cells which can be greatly enriched for FoxP3, methods of expanding the isolated cells, pharmaceutical compositions of such cells, and methods of their use in the treatment of autoimmune and other immune system mediated disorders.