Autoantigenic HCgp39 epitopes are presented by the HLA-DM-dependent presentation pathway in human B cells.
J Immunol
; 166(1): 33-41, 2001 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-11123274
ABSTRACT
It is hypothesized that autoimmune diseases manifest when tolerance to self-Ags fails. One possible mechanism to break tolerance is presentation of self-Ag in an altered form. Most Ags are presented by APCs via the traditional presentation pathway that includes "epitope editing" by intracellular HLA-DM, a molecule that selects for stable MHC-peptide complexes. We were interested in testing the hypothesis that autoreactive MHC-peptide complexes may reach the cell surface by an alternate pathway without being edited by HLA-DM. We selected a cartilage autoantigen human cartilage glycoprotein 39 to which T cell responses are observed in rheumatoid arthritis (RA) patients and some DR(*)04 healthy subjects. RA is genetically associated with certain DRB1 alleles, including DRB1(*)0401 but closely related allele DRB1(*)0402 is either neutral or mildly protective with respect to RA. We generated human B lymphoblastoid cell line cells expressing DR(*)0401 or DR(*)0402 in the presence or absence of intracellular HLA-DM and assessed their ability to present a candidate autoantigen, human cartilage glycoprotein 39. Our results show that the presence of intracellular HLA-DM is critical for presentation of this autoantigen to CD4(+) T cell hybridomas generated from DR(*)04-transgenic mice. Presentation of an autoantigen by the traditional HLA-DM-dependent pathway has implications for Ag presentation events in RA.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autoantigens
/
B-Lymphocytes
/
Glycoproteins
/
HLA-D Antigens
/
Antigen Presentation
/
Epitopes, B-Lymphocyte
Limits:
Animals
/
Humans
Language:
En
Journal:
J Immunol
Year:
2001
Document type:
Article
Affiliation country: