Functionality of major histocompatibility complex class II molecules in mice doubly deficient for invariant chain and H-2M complexes

Functionality of major histocompatibility complex class II molecules in mice doubly deficient for invariant chain and H-2M complexes

^*Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, University Louis Pasteur 1, rue Laurent Fries, 67404 Illkirch, Strasbourg, France; and ^§Center for Cancer Research, Massachusetts Institute of Technology, E17-323, 40 Ames Street, Cambridge, MA 02139

Edited by Philippa Marrack, National Jewish Center, Denver, CO, and approved June 3, 1997 (received for review April 7, 1997)

Abstract

By combining two previously generated null mutations, Ii° and M°, we produced mice lacking the invariant chain and H-2M complexes, both required for normal cell-surface expression of major histocompatibility complex class II molecules loaded with the usual diverse array of peptides. As expected, the maturation and transport of class II molecules, their expression at the cell surface, and their capacity to present antigens were quite similar for cells from Ii°M° double-mutant mice and from animals carrying just the Ii° mutation. More surprising were certain features of the CD4⁺ T cell repertoire selected in Ii°M° mice: many fewer cells were selected than in Ii⁺M° animals, and these had been purged of self-reactive specificities, unlike their counterparts in Ii⁺M° animals. These findings suggest (i) that the peptides carried by class II molecules on stromal cells lacking H-2M complexes may almost all derive from invariant chain and (ii) that H-2M complexes edit the peptide array displayed on thymic stromal cells in the absence of invariant chain, showing that it can edit, in vivo, peptides other than CLIP.

Footnotes

↵ † Present address: The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099.
↵ ‡ Present address: Basel Institute for Immunology, Grenzacherstrasse 487, Postfach, CH-4005 Basel, Switzerland.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: MHC, major histocompatibility complex; ER, endoplasmic reticulum; Ii, invariant chain; APC, antigen-presenting cell; PNA, peanut agglutinin.