MHC multimer: A Molecular Toolbox for Immunologists

Abstract

The advent of the major histocompatibility complex (MHC) multimer technology has led to a breakthrough in the quantification and analysis of antigen-specific T cells. In particular, this technology has dramatically advanced the measurement and analysis of CD8 T cells and is being applied more widely. In addition, the scope of application of MHC multimer technology is gradually expanding to other T cells such as CD4 T cells, natural killer T cells, and mucosal-associated invariant T cells. MHC multimer technology acts by complementing the T-cell receptor-MHC/peptide complex affinity, which is relatively low compared to antigen-antibody affinity, through a multivalent interaction. The application of MHC multimer technology has expanded to include various functions such as quantification and analysis of antigen-specific T cells, cell sorting, depletion, stimulation to replace antigen-presenting cells, and single-cell classification through DNA barcodes. This review aims to provide the latest knowledge of MHC multimer technology, which is constantly evolving, broaden understanding of this technology, and promote its widespread use.

Keywords: MHC multimer; antigen-specific T cells.

Fig. 1. Classes of MHC multimers.

Three classes of MHC multimers used in the detection of various T cells are schematically depicted. Classical MHC multimers include MHC class I for CD8 T cells and MHC class II for CD4 T cells. Non-classical MHC multimers have been also developed and used for the detection of NKT cells, γδ T cells, and MAIT cells.

Fig. 2. Evolution of MHC multimers.

A schematic illustration is shown for the evolution of MHC multimer technology. It includes a variety of multimers in different geometry and valency (A), multimers with flexible loading capability (B), and variants for reversible binding (C).

Fig. 3. Application of MHC multimers.

A schematic illustration is shown for the application of MHC multimer technology, including cell enrichment or depletion (A), combinatorial detection in a single sample (B), antigen-specific T-cell stimulation and amplification using artificial antigen-presenting complex (C), and multi-parametric detection of rare T cells using mass cytometry with isotope-labeled MHC multimers or DNA barcoded MHC multimers (D).