MHC Class II Tetramers

Abstract

MHC Class II tetramers have emerged as an important tool for characterization of the specificity and phenotype of CD4 T cell immune responses, useful in a large variety of disease and vaccine studies. Issues of specific T cell frequency, biodistribution, and avidity, coupled with the large genetic diversity of potential class II restriction elements, require targeted experimental design. Translational opportunities for immune disease monitoring are driving rapid development of HLA class II tetramer use in clinical applications, together with innovations in tetramer production and epitope discovery.

Antigen-Reactive T Cell Enrichment for Direct, High-Resolution Analysis of the Human Naive and Memory Th Cell Repertoire

“…However, the MHC-multimer technology is limited to the previous knowledge of MHC alleles and antigenic epitopes. Due to the very high diversity of MHC molecules and especially for complex pathogens, containing hundreds or thousands of different target epitopes, choosing the right peptide-MHC combinations to study Ag-specific T cell responses is quite challenging (23). Furthermore, the restriction to few antigenic epitopes gives only limited and preselected insight into the heterogeneous T cell populations specific for a certain Ag.…”

Just the FACS

“…Len and colleagues further predicted, "our separation technique is specifically designed to detect and separate rare cells, and we ultimately hope to investigate the primary response by use of a virgin spleen-cell population enriched with antigen-binding cells." Today fluorochromelabeled MHC-peptide tetrameric complexes and FACS are routinely used to quantitate and isolate T cells from both naive and immunized mice and humans (9).…”

Tetramer-Guided Epitope Mapping: A Rapid Approach to Identify HLA-Restricted T-Cell Epitopes from Composite Allergens

“…HLA/ peptide complexes can engage αβTCR and permit the analysis of allergen-specific CD4 + T cells. The concept of using soluble HLA/peptide-labeled ligands to study these rare T-cell populations has been a successful strategy applied in numerous translational and clinical contexts [9]. As mentioned earlier, Class II tetramers can be used to identify novel T-cell epitopes.…”