Demonstration of T-Cell Monotypia Using Anti-TCRbeta1/2 (/2) Immunostaining as a Rapid and Cost-Effective Alternative to PCR-Based Clonality Studies for the Diagnosis of T-Cell Lymphoma.

Background/objectives: T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates, and diagnosis typically relies on slow, complex, and expensive multiplexed PCR reactions, requiring significant training and experience to interpret them. We aimed to raise highly specific antibodies against the two alternatively used and very similar T-cell receptor beta constant regions, TCRbeta1 and TCRbeta2, encoded by the and gene segments, respectively. We sought to demonstrate the feasibility of detecting TCRbeta1 and TCRbeta2 immunohistochemically in routine clinical (formalin-fixed, paraffin-embedded (FFPE)) tissue sections as a novel diagnostic strategy for T-cell lymphomas.

CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms.

The CD1 system binds lipid antigens for display to T cells. Here, we solved lipidomes for the four human CD1 antigen-presenting molecules, providing a map of self-lipid display. Answering a basic question, the detection of >2,000 CD1-lipid complexes demonstrates broad presentation of self-sphingolipids and phospholipids.

CD1a promotes systemic manifestations of skin inflammation.

Inflammatory skin conditions are increasingly recognised as being associated with systemic inflammation. The mechanisms connecting the cutaneous and systemic disease are not well understood. CD1a is a virtually monomorphic major histocompatibility complex (MHC) class I-like molecule, highly expressed by skin and mucosal Langerhans cells, and presents lipid antigens to T-cells.

Phospholipase activity of acyloxyacyl hydrolase induces IL-22-producing CD1a-autoreactive T cells in individuals with psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by Th17 responses. Recent evidence has identified Langerhans cells to have a key role in disease pathogenesis, with constitutive high expression of CD1a and capacity to present lipid antigens to T cells. Phospholipase A enzymes generate neolipid antigens for recognition by CD1a-reactive T cells; however, the broader enzymatic pathways of CD1a lipid ligand generation have not been thoroughly investigated.