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PMID: 3126253 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Structural mutation affecting intracellular transport and cell surface expression of murine class II molecules.

The Journal of experimental medicine ·Vol. 167 ·No. 2 ·1988-02-01 ·Pages 541-55

Griffith IJ, Nabavi N, Ghogawala Z, Chase CG, Rodriguez M, McKean DJ, Glimcher LH

Abstract

We have selected Ia variants from the Ia+ (H-2d) M12.4.1 B cell lymphoma that are negative on the cell surface for one or both Ia isotypes. The molecular analysis of two such independently selected cell lines, M12.A2 and M12.C3, is reported here. This analysis revealed that the genes encoding Ad beta (M12.A2) and Ed beta (M12.C3) contained identical single-nucleotide transitions that resulted in the substitution of Ser (mutant) for Asn (wild-type) at residue 82/83 of the extracellular NH2-terminal (membrane distal) beta 1 domain. This conservative substitution caused a cytoplasmic accumulation of I-A or I-E molecules in the respective cell line although predicted secondary-structure analysis suggests a minimal effect on protein conformation. Thus, the mutation appears to have either created a negative signal that stops transport or eliminated a positive signal that is required for transport and targeting to the cell surface.

MeSH Terms
Amino Acid Sequence Animals Antigenic Variation Antigens, Surface/analysis,genetics Base Sequence Biological Transport Body Fluids/metabolism Genes, MHC Class II Histocompatibility Antigens Class II/analysis,genetics Intracellular Fluid/immunology,metabolism Mice Mice, Inbred BALB C Molecular Sequence Data Mutation Peptide Fragments/genetics Protein Conformation
Chemicals
Antigens, Surface Histocompatibility Antigens Class II Peptide Fragments
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Griffith I J
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115.
Nabavi N
Ghogawala Z
Chase C G
Rodriguez M
McKean D J
Glimcher L H
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.167.2.541
Published
1988-02-01
Pages
541-55
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2188865
Subset
IM
Grants
NIAID NIH HHS · AI-21163 · United States
NIAID NIH HHS · AI-21569 · United States
NCI NIH HHS · CA-26297 · United States
External Links
PubMed source DOI: 10.1084/jem.167.2.541 PMC Full Text View journal details
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