Title
Bi-specific MHC heterodimers for characterization of cross-reactive T cells
Academic Program
Interdisciplinary Graduate Program
UMMS Affiliation
Department of Pathology; Department of Medicine, Division of Diabetes; Department of Biochemistry and Molecular Pharmacology
Publication Date
2010-10-22
Document Type
Article
Disciplines
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
Abstract
T cell cross-reactivity describes the phenomenon whereby a single T cell can recognize two or more different peptide antigens presented in complex with MHC proteins. Cross-reactive T cells have previously been characterized at the population level by cytokine secretion and MHC tetramer staining assays, but single-cell analysis is difficult or impossible using these methods. In this study, we describe development of a novel peptide-MHC heterodimer specific for cross-reactive T cells. MHC-peptide monomers were independently conjugated to hydrazide or aldehyde-containing cross-linkers using thiol-maleimide coupling at cysteine residues introduced into recombinant MHC heavy chain proteins. Hydrazone formation provided bi-specific MHC heterodimers carrying two different peptides. Using this approach we prepared heterodimers of the murine class I MHC protein H-2K(b) carrying peptides from lymphocytic choriomeningitis virus and vaccinia virus, and used these to identify cross-reactive CD8+ T cells recognizing both lymphocytic choriomeningitis virus and vaccinia virus antigens. A similar strategy could be used to develop reagents to analyze cross-reactive T cell responses in humans.
DOI of Published Version
10.1074/jbc.M110.141051
Source
J Biol Chem. 2010 Oct 22;285(43):33144-53. Link to article on publisher's site
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
PubMed ID
20729210
Repository Citation
Shen ZT, Brehm MA, Daniels KA, Sigalov AB, Selin LK, Welsh RM, Stern LJ. (2010). Bi-specific MHC heterodimers for characterization of cross-reactive T cells. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1074/jbc.M110.141051. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1685