A single amino acid substitution in an MHC class I molecule allows heteroclitic recognition by lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes

Daniel Muller, Katrina Pederson, Richard Murray, Jeffrey A Frelinger

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Class I molecules of the MHC bind foreign and endogenous peptides allowing recognition by the TCR on CTL. The recognition and killing of cells infected with lymphocytic choriomeningitis virus (LCMV) depends on the recognition of LCMV peptides bound to class IMHC. Mutations in class IMHC molecules have enabled the delineation of regions in the class I molecule important for binding peptides and for interaction with the TCR. We have constructed a library of class I mutants using saturation mutagenesis and report a phenotypic change resulting from a single amino acid substitution that results in the heteroclitic (increased) killing of LCMV-infected cells. This amino acid change, asparagine to serine at position 30, is in a conserved region of the class I molecule contacting the α3 domain. This mutation does not result in increased expression of the class 1 molecule on the cell surface, does not affect the binding of CD8, and does not affect allogeneic recognition. Cold target experiments show that this heteroclitic killing is due to increased recognition by CTL. These data point toward a critical function for this region of the class I molecule in the binding of peptides or their presentation to CTL.

Original languageEnglish (US)
Pages (from-to)1392-1397
Number of pages6
JournalJournal of Immunology
Volume147
Issue number4
StatePublished - Aug 15 1991
Externally publishedYes

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Lymphocytic choriomeningitis virus
Cytotoxic T-Lymphocytes
Amino Acid Substitution
Peptides
Mutation
Asparagine
Mutagenesis
Serine
Libraries
Amino Acids

ASJC Scopus subject areas

  • Immunology

Cite this

A single amino acid substitution in an MHC class I molecule allows heteroclitic recognition by lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes. / Muller, Daniel; Pederson, Katrina; Murray, Richard; Frelinger, Jeffrey A.

In: Journal of Immunology, Vol. 147, No. 4, 15.08.1991, p. 1392-1397.

Research output: Contribution to journalArticle

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