HLA Class Ib and MICA/MICB Expression in Human Tissues and Cell Types: Reshuffling Immune Players

Area of Science:

• Immunogenetics
• Molecular Biology
• Human Physiology

Background:

• Abnormal expression of Human Leukocyte Antigen (HLA) class Ib, MICA, and MICB molecules is linked to various pathological conditions.
• Understanding the comprehensive transcriptional expression of these genes across human tissues is crucial for deciphering their roles.

Purpose of the Study:

• To analyze the transcriptional expression of HLA class Ib, MICA, MICB, HLA class Ia, HLA class II, costimulatory molecules, and HLA transcription factors across diverse human organs and tissues at a single-cell level.
• To compare expression patterns and investigate potential non-immune functions of these molecules in non-immune cells and tissues.

Main Methods:

• Utilized RNA-sequencing data from two publicly available human projects.
• Analyzed gene expression at the single-cell level across various organs and tissues.
• Compared expression of 21 target genes, including HLA class Ia, Ib, II, costimulatory molecules, and transcription factors.

Main Results:

• Median gene expression varied by orders of magnitude, challenging the absolute distinction between classical and non-classical HLA genes based on expression.
• Lymphoid organs, lungs, and gastrointestinal tract showed the highest expression of HLA and related genes.
• Adipocytes, endothelial cells, and immune cells exhibited surprisingly similar expression patterns at the single-cell level.
• Expression in non-immune organs (lung, colon) and cells (adipocytes) suggests additional non-immune functions.
• Studied HLA transcription factors had limited impact on HLA regulation in non-immune tissues.

Conclusions:

• The classical/non-classical HLA classification based on structure and polymorphism does not fully extend to their expression patterns.
• Expression patterns in non-immune tissues indicate potential novel roles for HLA molecules beyond immune homeostasis.
• Further research is needed to identify additional HLA transcription factors regulating gene expression in non-immune tissues.