Invariant chain-independent function of H-2M in the formation of endogenous peptide-major histocompatibility complex class II complexes in vivo.
Efficient loading of major histocompatibility complex class II molecules with peptides requires the invariant chain (Ii) and the class II-like molecule H-2M. Recent in vitro biochemical studies suggest that H2-M may function as a chaperone to rescue empty class II dimers. To test this hypothesis in vivo, we generated mice lacking both Ii and H-2M (Ii-/-M-/-). Antigen presenting cells (APCs) from Ii-/-M-/- mice, as compared with APCs from Ii-/- mice, exhibit a significant reduction in their ability to present self-peptides to a panel of class II I-Ab-restricted T cells. As a consequence of this defect in the loading of self peptides, CD4(+) thymocyte development is profoundly impaired in Ii-/-M-/- mice, resulting in a peripheral CD4(+) T cell population with low levels of T cell receptor expression. These findings are consistent with the idea that H-2M functions as a chaperone in the peptide loading of class II molecules in vivo.
Kovats
S
S
Department of Immunology, University of Washington School of Medicine, Seattle 98195, USA.
Grubin
C E
CE
Eastman
S
S
deRoos
P
P
Dongre
A
A
Van Kaer
L
L
Rudensky
A Y
AY
D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D001324:Autoantigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics* / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000235:genetics
D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D010455:Peptides; C045084:invariant chain