Mutations in the α1 domain of a class I gene define residues important for specific allorecognition

Richard Murray, Kiyoshi Katoh, Jeff Alexander, Daniel Muller, Katrina Pederson, Jeffrey A Frelinger

Research output: Contribution to journalArticle

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Abstract

Our strategy to use saturation mutagenesis to produce an unbiased collection of major histocompatibility class I mutants has resulted in unpredicted mutant phenotypes. First, we have shown data supporting our earlier work of the DP20(Y27N) mutant. Allorecognition is altered at the clonal level while no variation in lymphocytic choriomeningitis virus (LCMV)-restricted recognition is observed. The defect does not destroy the integrity of this class I protein on the basis of three observations: (i) LCMV self-restricted recognition is not impaired, (ii) β2 microglobulin still associates with DP20(Y27N) at the cell surface, and (iii) this mutant can stimulate a primary MLR. Thus, we believe DP20(Y27N) specifically affects allorecognition, perhaps by altering self peptide associations. The DP14(A11V;E32Q) mutant appears to interact with T cell receptors (TCR) from a cloned cytotoxic T lymphocyte, but is altered in inducing a wild type signal into the responding cell. This is presumably due to decreased interaction at the cell surface between DP14(A11V;E32Q) and wild type-specific TCR such that variations are detected in how a cell perceives extracellular signals. Analysis of additional mutants suggests that mutant DP163(N66S) alters the binding site for monoclonal antibodies 7-16.10 and 135, while leaving unaltered the binding site for monoclonal antibodies 34-1.2 and 11-20.3. This maps the residue responsible for 7-16.10 and 135 binding to the region of DP163(N66S).

Original languageEnglish (US)
Pages (from-to)220-230
Number of pages11
JournalCellular Immunology
Volume128
Issue number1
DOIs
StatePublished - 1990
Externally publishedYes

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MHC Class I Genes
Lymphocytic choriomeningitis virus
T-Cell Antigen Receptor
Mutation
Binding Sites
Monoclonal Antibodies
Histocompatibility
Cytotoxic T-Lymphocytes
Cell Communication
Mutagenesis
Phenotype
Peptides
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Mutations in the α1 domain of a class I gene define residues important for specific allorecognition. / Murray, Richard; Katoh, Kiyoshi; Alexander, Jeff; Muller, Daniel; Pederson, Katrina; Frelinger, Jeffrey A.

In: Cellular Immunology, Vol. 128, No. 1, 1990, p. 220-230.

Research output: Contribution to journalArticle

Murray, Richard ; Katoh, Kiyoshi ; Alexander, Jeff ; Muller, Daniel ; Pederson, Katrina ; Frelinger, Jeffrey A. / Mutations in the α1 domain of a class I gene define residues important for specific allorecognition. In: Cellular Immunology. 1990 ; Vol. 128, No. 1. pp. 220-230.
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