PMID- 8700841
OWN - NLM
STAT- MEDLINE
DCOM- 19960905
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 93
IP  - 5
DP  - 1996 Mar 5
TI  - Immune response of HLA-DQ8 transgenic mice to peptides from the third 
      hypervariable region of HLA-DRB1 correlates with predisposition to rheumatoid 
      arthritis.
PG  - 1814-9
AB  - The major histocompatibility complex class II genes play an important role in the 
      genetic predisposition to many autoimmune diseases. In the case of rheumatoid 
      arthritis (RA), the human leukocyte antigen (HLA)-DRB1 locus has been implicated 
      in the disease predisposition. The "shared epitope" hypothesis predicts that 
      similar motifs within the third hypervariable (HV3) regions of some HLA-DRB1 
      alleles are responsible for the class II-associated predisposition to RA. Using a 
      line of transgenic mice expressing the DQB1*0302/DQA1*0301 (DQ8) genes in the 
      absence of endogenous mouse class II molecules, we have analyzed the antigenicity 
      of peptides covering the HV3 regions of RA-associated and nonassociated DRB1 
      molecules. Our results show that a correlation exists between proliferative 
      response to peptides derived from the HV3 regions of DRB1 chains and 
      nonassociation of the corresponding alleles with RA predisposition. While HV3 
      peptides derived from nonassociated DRB1 molecules are highly immunogenic in DQ8 
      transgenic mice, all the HV3 peptides derived from RA-associated DRB1 alleles 
      fail to induce a DQ8-restricted T-cell response. These data suggest that the role 
      of the "shared epitope" in RA predisposition may be through the shaping of the 
      T-cell repertoire.
FAU - Zanelli, E
AU  - Zanelli E
AD  - Department of Immunology, Mayo Clinic and Medical School, Rochester, MN 55905, 
      USA.
FAU - Krco, C J
AU  - Krco CJ
FAU - Baisch, J M
AU  - Baisch JM
FAU - Cheng, S
AU  - Cheng S
FAU - David, C S
AU  - David CS
LA  - eng
GR  - AI14764/AI/NIAID NIH HHS/United States
GR  - AI25150/AI/NIAID NIH HHS/United States
GR  - AR30752/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (HLA-D Antigens)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arthritis, Rheumatoid/*genetics
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - HLA-D Antigens/*immunology
MH  - Haplotypes
MH  - Humans
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Peptides/immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/metabolism
PMC - PMC39864
EDAT- 1996/03/05 00:00
MHDA- 1996/03/05 00:01
PMCR- 1996/09/05
CRDT- 1996/03/05 00:00
PHST- 1996/03/05 00:00 [pubmed]
PHST- 1996/03/05 00:01 [medline]
PHST- 1996/03/05 00:00 [entrez]
PHST- 1996/09/05 00:00 [pmc-release]
AID - 10.1073/pnas.93.5.1814 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1814-9. doi: 10.1073/pnas.93.5.1814.