Truncation of the class II beta-chain cytoplasmic domain influences the level of class II/invariant chain-derived peptide complexes.
Previous studies have established that antigen presenting cells (APC) expressing major histocompatibility complex class II beta chains with truncated cytoplasmic domains are impaired in their capacity to activate T cells. While it had been widely accepted that this impairment is due to a defect in class II cytoplasmic domain-dependent signal transduction, we recently generated transgenic mice expressing only truncated class II beta chains, and functional analyses of APC from these mice revealed signaling-independent defects in antigen presentation. Here, we demonstrate that T cells primed on such transgenic APC respond better to stimulation by APC expressing truncated beta chains than by wild-type APC. This finding suggests that APC expressing truncated class II beta chains are not inherently defective in their antigen presenting capacity but, rather, may differ from wild-type APC in the peptide antigens that they present. Indeed, analysis of the peptides bound to class II molecules isolated from normal and transgenic spleen cells revealed clear differences. Most notably, the level of class II-associated invariant chain-derived peptides (CLIP) is significantly reduced in cells expressing only truncated beta chains. Prior studies have established that CLIP and antigenic peptides compete for binding to class II molecules. Thus, our results suggest that the cytoplasmic domain of the class II beta chain affects antigen presentation by influencing the level of CLIP/class II complexes.
Smiley
S T
ST
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115, USA.
Rudensky
A Y
AY
Glimcher
L H
LH
Grusby
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry* / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D010455:Peptides; C045084:invariant chain