HLA class II-restricted binding of muramyl peptides to B lymphocytes of normal and narcoleptic subjects.
The propensity for narcolepsy, a clinical sleep disorder of unknown etiology, is virtually totally included within the HLA-DR2,DQw1 (DRw15,DQw6) phenotype. The disorder is characterized by decreased sleep latency, early onset of rapid eye movement sleep, and a paucity of nocturnal slow-wave sleep. Muramyl peptides, naturally occurring bacterial cell wall peptidoglycans, potently enhance the duration and amplitude of slow-wave sleep in animals, bind to murine mononuclear cells, and exhibit a major histocompatibility complex-restricted immunoadjuvant effect in mice. We examined the binding of muramyl peptides to peripheral blood mononuclear leukocytes of HLA-typed normal (n = 13) and narcoleptic (n = 10) subjects. Muramyl peptides bound specifically and with high affinity to normal B- but not T-lymphocyte-enriched preparations. There was no significant specific binding to B-cell-enriched preparations from narcoleptic patients. Furthermore, B-lymphocyte-enriched preparations of normal individuals who had the HLA-DR2,DQw1 phenotype (n = 8) exhibited a lower level of specific binding than those of normals who did not have this phenotype (n = 5, p less than 0.001). These observations are an additional indication of the relevance of muramyl peptides to slow-wave sleep and provide a basis for a better understanding of the relation between narcolepsy and the MHC at the biochemical level.
Silverman
D H
DH
Harvard Medical School, Boston, Massachusetts.
Sayegh
M H
MH
Alvarez
C E
CE
Johnson
T S
TS
Milford
E L
EL
Karnovsky
M L
ML
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000378:metabolism*; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D000119:Acetylmuramyl-Alanyl-Isoglutamine