Fq. Li et al., REDUCED EXPRESSION OF PEPTIDE-LOADED HLA CLASS-I MOLECULES ON MULTIPLE-SCLEROSIS LYMPHOCYTES, Annals of neurology, 38(2), 1995, pp. 147-154
Lymphocytes from patients with HLA class II-linked autoimmune diseases
such as type I diabetes, systemic lupus erythematosus, rheumatoid art
hritis, and Graves' have recently been shown to have a decrease in the
expression of self-peptide-filled HLA class I antigens on the surface
of peripheral lymphocytes. The human demyelinating diseases of multip
le sclerosis in some cases are also associated with the presence of ce
rtain HLA class II genes, which may in turn be linked to genes in the
class II region that control class I expression. Hence, we studied fre
sh peripheral blood mononuclear cells (PBMCs) and newly produced Epste
in-Barr virus (EBV)-transformed cell lines from multiple sclerosis pat
ients for the class I defect. Unseparated PBMCs, as well as T cells, B
cells, and macrophages from multiple sclerosis patients had a decreas
e in the amount of conformationally correct peptide-filled HLA class I
molecules on the cell surface compared with matched controls detectab
le by flow cytometry. To demonstrate the independence of this defect f
rom exogenous serum factors, newly produced EBV-transformed cell lines
from B cells of patients with multiple sclerosis maintained the defec
t. In addition, DR2 +/+, +/-, and -/- EBV-transformed B cells from the
se patients similarly demonstrated the self-antigen presentation defec
t. Analysis of a set of discordant multiple sclerosis twins revealed t
he class I defect was exclusively found on the affected twin lymphocyt
es, suggesting a role of this class I complex in disease expression. T
hese data indicate that multiple sclerosis patients have abnormal pres
entation of self-antigens. This phenomenon, common to a number of HLA-
linked autoimmune disorders, may be associated with failed self-tolera
nce and improper T-cell education secondary to faulty HLA class I asse
mbly controlled by HLA class II linked genes.