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PMID: 8098731 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression.

The Journal of experimental medicine ·Vol. 177 ·No. 6 ·1993-06-01 ·Pages 1699-712

Bikoff EK, Huang LY, Episkopou V, van Meerwijk J, Germain RN, Robertson EJ

Abstract

We used gene targeting techniques to produce mice lacking the invariant chain associated with major histocompatibility complex (MHC) class II molecules. Cells from these mice show a dramatic reduction in surface class II, resulting from both defective association of class II alpha and beta chains and markedly decreased post-Golgi transport. The few class II alpha/beta heterodimers reaching the cell surface behave as if empty or occupied by an easily displaced peptide, and display a distinct structure. Mutant spleen cells are defective in their ability to present intact protein antigens, but stimulate enhanced responses in the presence of peptides. These mutant mice have greatly reduced numbers of thymic and peripheral CD4+ T cells. Overall, this striking phenotype establishes that the invariant chain plays a critical role in regulating MHC class II expression and function in the intact animal.

MeSH Terms
Animals Antigens, Differentiation, B-Lymphocyte Antigens, Surface/analysis Biological Transport CD4-Positive T-Lymphocytes/cytology,immunology Cells, Cultured Hematopoietic Stem Cells/cytology,immunology Histocompatibility Antigens Class II/analysis,chemistry,genetics,metabolism,physiology Mice Mice, Inbred C57BL Mutation Peptide Fragments/metabolism
Chemicals
Antigens, Differentiation, B-Lymphocyte Antigens, Surface Histocompatibility Antigens Class II Peptide Fragments invariant chain
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bikoff E K
Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138.
Huang L Y
Episkopou V
van Meerwijk J
Germain R N
Robertson E J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.177.6.1699
Published
1993-06-01
Pages
1699-712
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191043
Subset
IM
Grants
NIAID NIH HHS · AI-19047 · United States
External Links
PubMed source DOI: 10.1084/jem.177.6.1699 PMC Full Text View journal details
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